Obesity and substance use disorders are rapidly growing problems throughout the world. Of the current mainstay therapies of diet, exercise, behavioral modification, surgery, and medications, drugs have the greatest risk for abuse and dependence. As each of these disorders share similar underpinnings mediated by the dopaminergic brain reward pathways, clinicians must seriously consider the safety of both the patient's physical and mental health when prescribing treatments. Specifically, balance and awareness of the factors involved in the variable abuse potentials of these prescribed medications is paramount. A cursory review of weight loss medications commonly used is performed with attention to FDA status, mechanism of action, and abuse potential. Concurrent strategies to minimize risk such as drug screening, ruling out doctor shopping, temporal considerations, monitoring for signs and symptoms of abuse and/or dependency, and a safety-tiered prescribing approach is also discussed in order to optimize best treatment practice. As the understanding of these disorders progresses along with the evolution of agreed nomenclature and awareness of compulsive behavioral disorders in general, greater safety and more appropriate interventions may be achieved. Further areas of research will help to elucidate nuances of the coocurrance and treatment of these disorders and perhaps guide drug research and development in the area of drug treatments of obesity.