The natural course of substance use disorders (SUDs) is varied, ranging from very positive outcomes reported in general population samples meeting alcohol abuse or dependence criteria to very negative outcomes in treatment-seeking patients. The following illicit substances are the most harmful: heroin, cocaine, (meth)amphetamine, and cannabis. The effects of taking opioids are multiple, including euphoria, analgesia, indifference to anticipated distress, drowsiness, decreased concentration, and constipation. Substitution treatment with long-acting opioid agonists, such as methadone, buprenorphine, or the combination of buprenorphine/naloxone, is available in a growing number of countries and has become the main treatment in many of these countries. This chapter reviews the evidence for anticonvulsants, antidepressants, antipsychotics and dopamine agonists, stimulant-like medications, disuliram, opioid agonists, and some miscellaneous medications. Medications for the treatment of cannabis dependence include: those that may attenuate the reinforcing effects of cannabis and those that directly prevent relapse to cannabis use after initial abstinence.