Despite decades of research, few medications have gained Food and Drug Administration (FDA) approval for the management of substance abuse disorder. The paucity of successful medications can be attributed, in part, to the lack of clearly identified neurobiological targets for addressing the core pathology of addictive behavior. Commonalities in the behavioral and brain processes involved in the rewarding effects of drugs and foods has prompted the evaluation of candidate medications that target neural pathways involved in both drug and eating disorders. Here, pharmacological strategies for the development of novel medications for drug addiction are presented in the context of potential overlapping neurobiological targets identified for eating disorders (e.g., obesity, overeating, binge-eating) and substance abuse. Mechanisms discussed in this chapter include modulators of the gut-brain axis (e.g., leptin, ghrelin, cholecystokinin, cocaine- and amphetamine-regulated transcript, and pancreatic peptides) and neurotransmitter systems (e.g., opioids, cannabinoids, dopamine, serotonin, and acetylcholine).