ObjectiveCocaine, which first made its appearance >1,000 yrs ago, is now widely used throughout the world. The physiologic responses to cocaine may cause severe pathologic effects. This review highlights the many critical care challenges resulting from these effects.DesignHistorical vignettes, epidemiologic factors, modes of preparation and delivery, and the physiologic and pharmacologic effects of these agents are presented.SettingCocaine causes intense vasoconstriction, which potentially causes damage to all organ systems. Examples of these toxicities are presented.PatientsThe adverse multisystem responses to cocaine exposure produce organ failure, which challenges diagnostic accuracy and therapeutic intervention. Organ system failure involves the brain, heart, lung, kidneys, gastrointestinal tract, musculature, and other organs. These harmful effects are additive to preexisting organ dysfunction.InterventionRecognition of associated cocaine injury alerts the physician that organ dysfunction is more likely to occur and to be more severe. Such anticipation helps plan for therapy in the critical care setting.Results and ConclusionsCocaine use is an expanding health hazard, despite intense governmental efforts to contain its distribution and use. Recognition of the signs and symptoms of cocaine toxicity help anticipate the subsequent organ dysfunction and implement earlier organ system support.