Psychiatry is a specialty where the application of pharmacogenomics approaches is made to the study of interindividual differences in response to antidepressants. It is highly applied for improving patient treatment. Major depressive disorder (MDD) is a common and complex disorder resulting from genetic and environmental interactions. Less than 40% of patients with MDD achieve remission, and even after several treatment trials, one in three patients do not fully recover from MDD. Many clinical and genomic association studies suggested that the catechol-Omethyltransferase (COMT) gene region was an important genetic locus for psychiatric disorders, because of the proposed relationship between its function in catecholaminergic neurotransmission and individual response to antidepressants, and vulnerability to psychiatric disorders. Although a number of COMT single nucleotide polymorphisms (SNPs) were observed, the Val108/158Met (rs4680) polymorphism in exon 4 resulted in a change in the enzyme structure which has been intensively investigated in relation to its role of enzyme activity and processes of prefrontal cortex functions in cognition. As serotonin interacts with dopamine and dopamine availability is influenced by COMT SNPs, an association between the COMT gene and response to treatment, based on the various pharmacogenetics/pharmacogenomics studies about COMT gene published to date, is explored in this overview.