The enzyme catechol-O-methyltransferase (COMT) transfers a methyl group from S-adenosylmethionine to the benzene ring of catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. This review focuses on the association between the genetic polymorphisms of COMT gene and psychiatric disorders.