Cocaine addiction is a serious public health problem for which there is no Food and Drug Administration–approved pharmacological treatment. Psychotherapy remains the primary mode of treatment; however, relapse rates are high. Rather than reviewing all the pharmacotherapy studies done in the field of cocaine dependence, this chapter focuses on those that have shown the most promise. Importantly, the search for effective pharmacological treatment has yielded some positive signals in proof-of-concept trials for topiramate, modafinil, disulfiram, and ondansetron. These medications are being tested in confirmatory trials. Preclinical data and early clinical pilot data suggest that vigabatrin, cannabinoid-1 antagonists, dopamine D3 partial agonists, and corticotropin-releasing factor antagonists are promising therapeutic strategies. Immunotherapy is another promising approach, and early data from the cocaine vaccine trial are encouraging and are being pursued for further development.