Drug addiction is a serious relapsing disease that has high costs to society and to the individual addicts. Treatment of these addictions is still in its nascency, with only a few examples of successful therapies. Therapeutic response depends upon genetic, biological, social, and environmental components. A role for genetic makeup in the response to treatment has been shown for several addiction pharmacotherapies. For several addiction pharmacotherapies, response to treatment varies based on individual genetic makeup. In this chapter, we discuss the role of genetics in pharmacotherapies, specifically for cocaine, alcohol, and opioid dependences. The elucidation of the role of genetics should aid in the development of new treatments and increase the efficacy of existing treatments.