OBJECTIVE To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of duloxetine for the treatment of major depressive disorder (MDD). DATA SOURCES Searches using MEDLINE and PsycINFO were conducted (1966 to November 2003). STUDY SELECTION AND DATA EXTRACTION All duloxetine MDD information gathered was considered. Articles containing comprehensive information regarding duloxetine use for MDD were evaluated. DATA SYNTHESIS Duloxetine is a serotonin–norepinephrine reuptake inhibitor being considered for treatment of MDD and stress urinary incontinence. While approved dosing ranges have not yet been determined, studies support the efficacy and safety of 40–60 mg twice daily for the treatment of acute MDD. Adverse effects have been of mild to moderate severity and are considered to be transient. Cardiovascular effects (increased heart rate or blood pressure), while present, do not appear to be clinically significant. Overall, duloxetine appears to be well tolerated. CONCLUSIONS Duloxetine is a safe and effective antidepressant. Approval of this agent provides another treatment option for the management of MDD. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-036-H01