Cocaine dependence is a complicated, destructive, and often chronic illness that is difficult to treat. In this article we review the challenges in treating cocaine dependence, as well as recent developments and future directions in psychosocial and pharmacological treatment relevant to treatment of cocaine dependence. Cocaine is one of the most addictive drugs because of its immediate and powerful rewarding effects. Often, cocaine dependent individuals experience difficulty abstaining due to cognitive impairments from repeated cocaine use, strong use-related social and environmental cues, and high levels of life stress. Cocaine use also affects areas of the brain related to motor function, learning, emotion, and memory, further complicating the administration of effective interventions. In addition, development of treatments for cocaine dependence has been complicated by the tendency for abusers not to complete treatment programs and their propensity for relapse. Despite these challenges, some treatment approaches, such as cognitive behavioral therapy (CBT) and medications have shown promise in successfully treating cocaine dependence. However, individually, each of these treatments exhibit weakness in longitudinal studies where long-term abstinence is the primary outcome of interest. Although other treatments are being explored, thus far, the combination of CBT and pharmacotherapy has elicited the best results for treating cocaine dependence with respect to patient retention and relapse prevention following abstinence. No treatment method has yet been shown to completely and effectively treat cocaine dependence. More research is necessary to test treatment programs and garner further information in order to better understand and treat cocaine dependence.