A better understanding of the neurobiological substrates of alcohol and tobacco dependence has been accompanied by the increasing role of pharmacological relapse prevention. In alcohol dependence, substances which are able to block or ameliorate alcohol craving improve the maintenance of abstinence in combination with psychosocial treatment. In particular, the N-methyl-D-aspartate receptor antagonist acamprosate and the opiate receptor antagonist naltrexone have been shown to be effective in numerous trials. Administration starts immediately after detoxification and should last for 12 months. This treatment, however, is not a replacement for the psychosocial treatment of the alcohol dependence. Compared with placebo treatment, approximately twice as many patients remain abstinent under acamprosate 1 year after the end of treatment. The most widely studied and used pharmacotherapy for the treatment of tobacco dependence is nicotine containing medications. Nicotine replacement therapies (patch, gum, tablet, inhaler) have been shown to reduce tobacco craving and enhance abstinence. The only non-nicotine medication that has been approved in Germany is the antidepressant bupropion. Current studies identify particularly suitable subgroups of patients responding to more individualized pharmacological relapse prevention. A specific application of these substances will optimise the outcome for alcohol and tobacco dependent patients.