P-glycoprotein (P-gp), the gene product of ABCB1, is a drug transporter at the blood-brain barrier and could be a limiting factor for entrance of antidepressants into the brain, the target site of antidepressant action. Animal studies showed that brain concentrations of many antidepressants depend on P-gp. In humans, ABCB1 genotyping in the treatment of depression rests on the assumption that genetic variations in ABCB1 explain individual differences in antidepressant response via their effects on P-gp expression at the blood-brain barrier. High P-gp expression is hypothesized to lead to lower and often insufficient brain concentrations of P-gp substrate antidepressants. In this review, we summarize 32 studies investigating the question of whether ABCB1 polymorphisms predict clinical efficacy and/or tolerability of antidepressants in humans and evaluate the clinical application status of ABCB1 genotyping in depression treatment.