The proper use of antidotes in the intensive care setting when combined with appropriate general supportive care may reduce the morbidity and mortality associated with severe poisonings. The more commonly used antidotes that may be encountered in the intensive care unit (N-acetylcysteine, ethanol, fomepizole, physostigmine, naloxone, flumazenil, sodium bicarbonate, octreotide, pyridoxine, cyanide antidote kit, pralidoxime, atropine, digoxin immune Fab, glucagon, calcium gluconate and chloride, deferoxamine, phytonadione, botulism antitoxin, methylene blue, and Crotaline snake antivenom) are reviewed. Proper indications for their use and knowledge of the possible adverse effects accompanying antidotal therapy will allow the physician to appropriately manage the severely poisoned patient.