Cocaine produces a pattern of cardiovascular responses that are associated with apparent myocardial ischemia, arrhythmias, and other life-threatening complications in some individuals. Despite recent efforts to better understand the causes of cocaine-induced cardiovascular dysfunction, there remain a number of unanswered questions regarding the specific mechanisms by which cocaine elicits hemodynamic responses. This review will describe the actions of cocaine on the cardiovascular system and the evidence for the mechanisms by which cocaine elicits hemodynamic and pathologic responses in humans and animals. The emphasis will be on experimental data that provide the basis for our understanding of the mechanisms of cardiovascular toxicity associated with cocaine. More importantly, this review will identify several controversies regarding the causes of cocaine-induced cardiovascular toxicity that as yet are still debated. The evidence supporting these findings will be described. Finally, this review will outline the obvious deficits in our current concepts regarding the cardiovascular actions of cocaine in hope of encouraging additional studies on this grave problem in our society.