Tardive dyskinesia is a potentially fatal side effect of antipsychotics. In the classic form is characterized by involuntary hyperkinetic movements, especially those affecting the mimic and mastication muscles. The main hypothesis considers that the pathophysiological basis of the disorder is an overexpression of D2 receptors in the striatum, in response to dopamine block neuroleptics-mediated, especially the older ones. Because fortunately not all patients undergo this severe adverse effects, many efforts have been conducted in trying to delineate the risk factors so as to try to prevent tardive dyskinesia by administering lower doses of neuroleptics in vulnerable groups. Advanced age, female sex, smoking habits, diabetes mellitus, alcohol abuse are known as risk factors. The instead the role of the type of psychiatric disorder, instead, is still debated. Since there was a direct relationship between cumulative dose of antipsychotic and treatment duration, recent studies are aimed at identifying factors that contribute to increased plasma concentrations of the drug, such as genetic polymorphisms of metabolizer enzymes that encode for enzymatic variants with decreased activity.