The paucity of research on gender-specific differences related to antidepressants is a significant public health deficiency and represents an understudied and necessary research area. The current data suggest that the pharmacokinetics of antidepressant drugs can be substantially different between men and women as a result of differences in both the metabolizing enzymes and the expression of P-glycoprotein MDR1. The data suggest that different pharmacodynamic responses are observed between premenopausal women and men. Women are more likely to respond better to an MAOI antidepressant compared to men. In addition, men respond better to TCAs than women in this age group, but differences diminish after menopause. Given the evidence of distinct gender-specific differences, it is critical that these differences be addressed more widely in research evaluating the administration of antidepressants in women.