Several lines of evidence support a role for serotoninergic (5-HT) system abnormalities in the pathogenesis and treatment of several psychiatric disorders. This review summarizes information about the association between the 5-HT2A receptor gene and its relevance to schizophrenia, tardive dyskinesia, major depression, suicidality, anorexia nervosa and obsessive-compulsive disorder. Evidence is presented that implies that selective 5-HT2A antagonists may be considered useful in investigating the role of 5-HT2A receptor function and in the treatment of psychosis, and possibly alcohol and cocaine dependence. Additionally, findings are reviewed on the importance of 5-HT2A receptor antagonism in contributing to the therapeutic effect of several clinically effective and potential atypical antipsychotics as well as several antidepressants. In conclusion, the ability of selective 5-HT2A receptor antagonists to interfere with the heightened state of dopamine activity without altering basal tone, suggests that these drugs possess antipsychotic activity and may provide the basis for new therapies for psychosis and drug dependence, in addition to contributing towards a more complete understanding of 5-HT2A receptor function.