Cocaine use and abuse continue to overwhelm urban economic, social, and health care systems. Patients frequently present to the emergency department with life-threatening manifestations of cocaine use, including trauma, acquired immune deficiency syndrome, psychomotor agitation, and cardiovascular collapse. Adequate treatment of the cocaine-intoxicated patient requires a critical understanding of the risk-to-benefit ratios for pharmacologic, toxicologic, and surgical or obstetric interventions. The pharmacologic and physiologic bases for the vascular manifestations of cocaine toxicity and experimental evidence for treatment strategies are reviewed.