In addition to subjects with recurrent major depressive disorder (MDD), individuals with only a single episode of major depression were considered affected, as were those with bipolar disorder. One approach to potentially improving genetic linkage signals is to attempt to reduce genetic heterogeneity through reducing clinical heterogeneity. Studies of gene expression in MDD have been carried out in brain samples and in white blood cell samples from MDD patients, as well as in experimental cell lines and in mouse models. As with the genetics of MDD, the genetics of antidepressant response is likely to involve large numbers of genetic variations acting jointly to influence the phenotype. Epigenetic studies should advance our understanding of the mechanisms that underlie gene expression. Pharmacogenetic studies could also provide exciting clinical benefits from genetic investigations of MDD. Understanding of the basic processes would guide the search for novel treatments of MDD.