The player assumes the role of Ramiro "Ram" Cruz; criminal turned Drug Enforcement Agent. He has been sent into the Mexican border city of Los Toros and its surroundings by his twin brother Tommy, who wants him to find out who killed their father Ernesto. The player will be tasked with infiltrating and taking down the biggest drug cartel in Mexico and battling it out with dope dealers, bandidos, corrupt Federales and Mexican Army, loco luchadores, guerillas, and other asorted bad guys. Between story missions the player can do optional challenge missions as he or she wishes, exploring Los Toros and gathering bonuses to rack up a high score.
Ramiro "Ram" Cruz
The playable character for most of the game. Ramiro was in jail on multiple felonies, but then the DEA got him out to take his twin brother's place taking on the criminal elements of Los Toros. Ram does not believe in being careful, playing by the rules, or letting his enemies live very long. During the game, Ram is given the nickname "Gringo Loco" by the enemies he faces. Ram also calls himself "Gringo Loco" on occasion in the game as well.
Tomas "Tommy" Cruz
Ram's twin brother, playable for the second mission only. Tommy is a high-ranking DEA agent who has been trying to take down the Morales Cartel and clear his father's name. However his mission is quickly abandoned as his suffers major injures, due to a grenade. Instead his brother Ram must do it. Tommy does help some via a radio link through which he provides advice Ram may or may not take. On the Chili Con Carnage site, Tommy is seen as Ernesto's profile pic. It is unknown if this was accidential or not.
The boys' father, playable for the first mission only. A deep-cover DEA agent who unfortunately fell victim to a corrupt group of D.E.A. who pushed him out of a plane. Ernesto's death in Total Overdose is related to the "Overdose" portion of the game's title.
A mysterious drug lord who is responsible for the death of Ernesto Cruz and countless others. His true identity is unknown, and you will spend most of the game hunting him down but will never meet him.
Tommy's boss, who is not too thrilled with Ram being sent to handle things.
Marco the Rat
Owner of Marco's Junkyard in Los Toros. After Ram bails him out of trouble with the Virgilio he becomes a valuable asset.
Head of the notorious Morales Cartel, he runs most of the drug traffic in Los Toros, though he faces increasing competition from the Virgilio Cartel. He also owns a meat packing plant, a trucking company, and a shipping business. Not to mention the fact that he's the Los Toros Bullfighting Commissioner.
Cesar Morales's beautiful chauffeur/enforcer. She is actually a police officer and also helps out Ram.
Special Agent Johnson
Former partner of Ernesto, a highly trained veteran DEA agent who has put a lot of work into the Papa Muerte case seemingly with little result. Also known for his cowboy hat and John-Wayne-style modus operandi. He is an informer for General Montanez and responsible for Ernesto's death.
Special Agent Piersson
Another veteran DEA agent who worked with Ernesto. A good friend to Tommy and Ram but was killed in the ambush set by Papa Muerte.
A corrupt high-ranking leader of the Mexican army who has worked with the CIA and DEA but is currently employed by Papa Muerte.
Wealthy playboy thug, good friend of Cesar Morales, also a heavy dealer in arms and automobiles. Ram raids his base in a speedboat, which crashes into a pool. Elvez seemed to be caught by suprise and was forced to cooperate, but just as Ram turns back he attempts to ambush the player as a revenge, due to the fact that Ram got his car shop destroyed. It is known that he was propared for Ram's raid because the two girls that was with him has hidden assault rifles beneath the hot tub. However he was killed during the raid.
Your basic weapon. Always with you, always useful. Note that your method of using them changes depending on your angle to the enemy. You can punch, kick, elbow smash, groin stomp, head butt, and do all kinds of dirty smackdowns.
Iron bar, baseball bat, rake, shovel, machete, etc. Grab these to increase your hand-to-hand skills.
The most common weapon. Ammo is plentiful and guns are accurate.
It holds less ammo than the pistol and is bit rarer, but its shots are more powerful.
Like the pistol it's quite plentiful. Very powerful but runs out of ammo quick. Short Range.
Packs more ammo than the Sawn-Off Shotgun, and can't be dual-wield like the sawn-off shotgun.
Submachine Gun (SMG)
MP5s, Uzis, Ingrams. These hold lots of ammo and are great for spraying around while shoot dodging. The smaller ones can be dual-wielded once you have enough Weapon Skill.
Your basic long range gun, usually found in the hands of enemies. You can get Hunting Rifles or basic Rifles- which can be Dual Wielded with enough Weapon Skill.
AK47s or modern M4s. Long range with rapid fire.
Grenades and Other Explosives
Grenades, Dynamite, Molotov Cocktails. All useful, all available. Note that the Grenades and Dynamite bounce when you throw them so be careful. You can also shoot them while they're in the air for maximum effect.
This gun launches bouncing explosives over a long distance.
Heavy damage, very hard to find. Will blow up most any structure or vehicle in one shot. Be careful you're not nearby when the shell impacts.
These can be found in freeroam and some missions on high places overlooking the street.
 Loco moves
These moves are special attacks you can pick up by scoring large amounts of points and combo kills. Use them wisely to eliminate particularly tough foes (like bosses) and/or groups of enemies. Note that you are invincible for a limited time while executing a Loco Move. The time the loco move lasts is EQUAL to your maximum health when it begins, but the time of the locomove drains during the use of it.
You receive a literally golden gun with four bullets that are automatically lethal to all enemies except bosses. This weapon does NOT give the headshot combo message like the other weapons capable of doing a headshot due to it being an auto-headshot weapon which the lack of the headshot combo message also applies if used from two shots to its four rounds during a "walk-walk" (running jump off the wall; a headshot during the Walk Walk is either called Fly on the wall or King of the Wall depending if you get the headshot while running on the wall or during the flip off the wall). Ram can be harmed during this loco move.
Ram spins around firing twin submachine guns and takes down all enemies in a 360 degree radius. Sometimes Ram will shout "Huracan Ramirez!!" after accomplishing this move. It is an easy way to get the uzis in your inventory.
Ram lowers his head like a bull and runs around in an automatic forward motion. Anybody he bumps into dies. It is ineffective if the enemy is in an area out of the reach of Ram during the Loco move (for example an enemy on the higher level that Ram is unable to reach Before, during and after the Loco move is used.).
This special move gives you two guitar cases with machine guns with infinite ammunition hidden inside. The attack is an obvious ode to the Mariachi Trilogy.
Sombrero of Death
This move creates a computer controlled sombrero-wearing zombie wielding a grenade launcher who will help you eliminate your foes. The zombie is invincible for the duration of the move, but Ram is not, which makes this loco move one of the three loco moves that leaves Ram vulnerable for attack during use. Ram can also be damaged by the grenades, making this one of the two moves Ram is vulnerable to friendly fire.
Explosive Piñata When used the enemy is distracted by the piñata (which is either a duck or goat) which can be shot or left to explode on its own. When it explodes, it takes out the enemies that went near it and humorously showers confetti during the aftermath of the explosion.
This move summons Numero Cinco, a powerful luchador wielding a random melee weapon. In Chili Con Carnage he is replaced by El Gimpo. Ram is vulnerable to attack during this loco move, and can even be damaged by the mad wrestler's melee attacks.
 Special vehicles
In the game, there are several vehicles found throughout the missions. Most of them can be found in free roam around Los Toros.
Joey Virgilio's "Conquistador"
Red with a black stripe in color and a protruding engine from the bonnet. This vehicle is nicknamed the "DeLoros" by fans due to its slight resemblance to a (heavily modified) DeLorean Motor Car. This car appears early on in the game and is possibly the fastest custom car in the game. Unfortunately, at the end of the mission in which it appears, the player must give it up. Made more unfortunate since the player had to keep the car in good condition as an element of this particular mission. However, this car can be found in free roam on the curve of the small stretch of road leading to Angel's Apartment. This car is considered excellent for making the big jumps to get any high bonuses.
Caesar Morales' Orange Dirtbike
After killing the Morales character and escaping from his exploding bull-ring on the said dirtbike, it will be parked outside the bull-ring ready for the player to take when they want. Like most cars in the game it will always spawn there, even if the player is already driving it.
Angel's Purple And Flame Pickup
This car is available to drive in free roam as well. Although, it's a little bit more complex to get this vehicle. To find it, the player must first, go to end of the tunnel near Angel's flat where there are cars overlooking the cliff, one of these cars will be a rusty pickup like Angel's. Steal this car and drive to, then through, the magic of sharp eyes and spawning you should see Angel's pickup parked somewhere (unfortunately without the Gun Turret on the back) for you to take when ever you want. Like most cars this will spawn in many places even when you're driving it. Ram has possession of the car in the intro of the game as well in Chili Con Carnage, causing speculation if Ram or Angel own the car or share it.
Marco's Tow Truck
After being used in a mission Marco's tow truck is always available at his junkyard.
After completing the game, it is possible for the player to get back to the DEA just by traveling along the side of a hill near the toll-gates while keeping close to an invisible barrier then the player will be able to find a Police Car to drive. In the PC version, there are also drivable Police Cars in El Centro, parked along the beach expressway from the gas station. Also sometimes at the cliff near angel's apartment where the two cars are parked, the van sometimes is a police van, but other times it's just a rusted beat up one.
DEA and Military SUVs
These may be found in in later missions, and in free roam in random locations after certain story missions. These are most often locked, but it's possible to shoot the driver out of a cruising DEA or Military vehicle, and then take possession of the vehicle and drive around with the broken windows. These can take more impacts and gunfire than many other vehicles in the game, but like any other vehicles will explode on contact when Ram leaps from it while it's in motion.