Psychiatric diseases that are treated with antidepressants are the leading causes of morbidity and mortality in humankind. Although antidepressants are generally well tolerated and widely available, they are not equally effective in all patients and only 35 - 45% of patients treated for depression with these drugs recover to premorbid levels of functioning. There is a need for an effective, individualized approach to antidepressant selection. One promising lead in the development of personalized medicine is the emerging field of pharmacogenomics, whereby pharmacologic agents are selected on the basis of the genotype of patients, with particular attention to drug targets and phase I- and phase II-metabolizing enzymes. This review article focuses on phase I antidepressant-metabolizing enzymes (e.g., relevant CYP enzymes). The authors first briefly review CYP nomenclature, the relevant members of the CYP superfamily and their alleles, the metabolic categories and CYP antidepressant substrates, inhibitors and inducers. The literature on the impact of CYP polymorphisms on antidepressant metabolism are also reviewed.