Antipsychotic medications, which comprise one of the most widely prescribed medication classes, have proven effective in many psychiatric conditions. However, these agents can also be associated with obesity and other metabolic abnormalities, the mechanisms of which have been partially elucidated. We review here the current state of knowledge of the effects of these medications on weight and appetite, as well as genetic markers that may help predict weight gain and prevent the undesirable cardiometabolic effects of these agents. Clinical Pharmacology & Therapeutics (2011) 90 1, 179–183. doi:10.1038/clpt.2011.97