The field of pharmacologic addiction treatment is expanding rapidly. While there are currently several FDA-approved medications for nicotine, alcohol, and opiate dependence, research into novel pharmacological approaches for these and additional substances is legion. Each drug of abuse, while sharing a common final neural pathway of increasing dopaminergic tone, has unique and individual characteristics that are important in developing improved and varied treatments. In this chapter, we discuss such research and present the neurobiological underpinnings of these explorations. In general, addiction treatment is focused on four areas: (1) reducing withdrawal discomfort, (2) diminishing cravings, (3) blocking rewarding effects of the drug, and (4) treating comorbidities, such as depression or ADHD. We present current ideas in pharmacologic research for nicotine, alcohol, cannabis, stimulants, and opiates.