Desvenlafaxine (DESV) is a newer antidepressant, which inhibits serotonin-norepinephrine reuptake neurotransmission, similarly to venlafaxine, milnacipran and duloxetine. It was approved in February 2008 by the FDA for the treatment of major depressive disorder (MDD), based on well-controlled and adequately powered, large clinical trials demonstrating efficacy and safety for patients with MDD. Currently available data show that DESV has proven efficacy, acceptable safety and tolerability profiles, convenient once-daily dosing and minimal impact on the cytochrome P450 enzyme system in patients with MDD. This mini-review summarizes the clinical data and practical use of DESV under this approved indication.