So far, there is increasing evidence of the active role of molecular biology in the psychiatric nosology as well as in the identification of psychiatric fenotypes. In this respect, the neurotransmitter serotonin (5-HT) has been involved in the etiopathogeny of multiple psychiatry conditions, such as affective disorder, schizophrenia, panic disorder, obsessive-compulsive disorder, alcoholism, eating disorder and personality disorder. The 5-HT2 receptor family includes the subtype 5-HT2A, a G protein coupled receptor whose activation leads to the stimulation of the enzyme phospholipase C and to the subsequent hydrolysis of the membrane located phosphoinositides, with the synthesis of the second messengers inositol triphosphate and diacylglicerol. This paper includes a review of the main findings concerning the polymorphism of the 5-HT2A in psychiatric disorders.