This chapter covers nicotine and alcohol dependence for evidence-based pharmacotherapy. First-line pharmacological interventions include varenicline as probably the most effective treatment, directly followed by nicotine replacement therapy (NRT) and bupropion. Second-line treatments include nortryptiline and clonidine with good effect sizes, but a higher probability of side-effects. Combining different types of NRT and the combination of NRT with other effective medications may result in better outcomes. Different kinds of medication are currently available for the treatment of alcohol dependence with different goals and different mechanisms of action, e.g. creation of aversive reaction to alcohol by blocking the metabolism of ethanol (disuliram), by reducing the positive reinforcing effect of alcohol (e.g. naltrexone), or the reduction of craving and the negative reinforcing effect of alcohol (e.g. acamprosate). The chapter discusses the findings regarding baclofen, gamma hydroxybutyric acid (GHB), and various types of antidepressants.