Acute delirium is a transient state of cerebral dysfunction reflecting an underlying medical decompensation. Toxicity from medications and other substances are a common cause of delirium. History and laboratory testing may be limited by alteration and lack of specific tests for certain compounds. Classes of compounds produce a constellation of symptoms and examination findings recognized as a toxidrome. Cessation of the offending agent, supportive care, and specific antidotal therapy are key to treatment. This article reviews the presentations of the anticholinergic toxidrome, sympathomimetic toxidrome, hallucinogenic toxidrome, γ-aminobutyric acid withdrawal, and Wernicke encephalopathy, as well as their mechanisms and basic management.