Toxicologic conditions are encountered in critically ill patients due to intentional or unintentional misuse of or exposure to therapeutic or illicit drugs. Additionally, toxicities related to medical interventions may develop in hospitalized patients. This review focuses on recent developments in the field of critical care toxicology. Early interventions to decrease absorption or enhance elimination of toxins have limited value. Specific interventions to manage toxicities due to analgesics, sedative-hypnotics, antidepressants, antipsychotics, cardiovascular agents, alcohols, carbon monoxide, and cholinergic agents are reviewed. Hospital-acquired toxicities due to methemoglobinemia, propylene glycol, and propofol should be recognized and treated. The clinician is continually required to incorporate clinical judgment along with available scientific data and clinical evidence to determine the best therapy for toxicologic conditions.