Despite the fact that more people seek treatment for cannabis-related disorders than for any other illicit substance-related disorder in the U.S., there are no medications approved for the treatment of these disorders. Similarly, more than half of those meeting criteria for a cocaine use disorder seek treatment. Yet, after two decades of intense medications development research efforts, there remains no approved cocaine pharmacotherapy. This paper reviews data from recent research investigations that may be relevant for the development of pharmacotherapies for cannabis- and cocaine-related disorders. Included in the discussion are findings from studies that have assessed the ability of medications to ameliorate cannabis- and cocaine-related abstinence symptoms in laboratory animals and human research participants. Data from studies that have investigated the effects of pharmacological agents on response to cannabis and cocaine are also reviewed because these data may provide information critical for informing relapse prevention medication development efforts. The majority of published studies evaluating cannabis pharmacotherapies have focused on decreasing withdrawal symptoms: a growing number of medications reduce symptoms in laboratory animals, but the majority of these findings have not been replicated in humans. Fewer studies have assessed the effects of potential cannabis treatment medications on cannabinoid-related reinforcing effects. In laboratory animals, only one has shown promise, while in humans, no medication has been demonstrated to alter marijuana self-administration behavior. Numerous medications have been examined for treating cocaine use disorders; in general, none have proven effective. Some medications, however, have demonstrated utility within subpopulations of cocaine-dependent individuals, suggesting that like psychosocial treatment, pharmacotherapy may need to be tailored to the individual.