The chemistry, pharmacology, and pharmacokinetics of cocaine are described, and the medical complications of illicit cocaine use are reviewed. Cocaine is readily absorbed from mucous membranes, the gastrointestinal tract, and the vascular beds of the lungs. Thus there are a number of routes for illicit cocaine administration, with the most popular one being intranasal. The most prevalent problems associated with the use of cocaine appear to be route and dose independent and are cardiovascular in nature; they include myocardial infarction and ischemia, sudden death, cardiac arrhythmias, and hypertension. Seizures, cerebrovascular accidents, hepatotoxicity, rhabdomyolysis, pulmonary complications, and obstetrical complications have also been reported. Gastrointestinal complications and acute toxicity may occur in cocaine smugglers who ingest cocaine-filled packets. Route-dependent complications of cocaine use are also of concern. The mechanism underlying the medical complications has not been fully elucidated but appears to be an extension of the drug's pharmacological properties. The treatment of cocaine-related toxicities is supportive and is based on the organ system affected. Drugs such as propranolol, labetalol, and nitrendipine have been advocated for treating the cardiovascular complications, and measures such as maintaining arterial blood pH, monitoring core body temperature, and diazepam therapy have been used to manage seizures. As the number of case reports of cocaine toxicity increases and the underlying mechanism is conclusively defined, management of the medical complications will improve.