The development of pharmacotherapies for cocaine addiction has been disappointingly slow. However, new neurobiological knowledge of how the brain is changed by chronic pharmacological insult with cocaine is revealing novel targets for drug development. Certain drugs currently being tested in clinical trials tap into the underlying cocaine-induced neuroplasticity, including drugs promoting GABA or inhibiting glutamate transmission. Armed with rationales derived from a neurobiological perspective that cocaine addiction is a pharmacologically induced disease of neuroplasticity in brain circuits mediating normal reward learning, one can expect novel pharmacotherapies to emerge that directly target the biological pathology of addiction.