Pharmacogenetic studies in mood disorders are rapidly proliferating after the initial reports linking gene variants to treatment outcomes. However, a considerable range of methodologies has been used, making it difficult to compare results across studies and limiting the representativeness of findings. Specification of sampling source (inpatients vs outpatients, primary vs tertiary settings), standardization of diagnostic systems and treatments, adequate monitoring of compliance through plasma levels, sufficient length of observation (at least 6 weeks for acute antidepressant treatments, though 3-6 months are preferable), the use of a range of response criteria and the inclusion of possible environmental confounding variables (life events, social support, temperament) are all potentially important issues when planning pharmacogenetic studies. We reviewed the state-of-the-art methodology and suggested possible guideline for future studies.