Vilazodone is a novel antidepressant with a dual mechanism of action that combines selective serotonin reuptake inhibition and partial 5-hydroxytryptamine1A receptor agonism. Vilazodone is undergoing clinical development for the treatment of major depressive disorder and has demonstrated antidepressant efficacy. In addition, in a placebo-controlled, randomized study, vilazodone has been shown to be well tolerated with a low discontinuation rate due to adverse events. Importantly, in this study, the incidence of sexual dysfunction with vilazodone was similar to that of the placebo. A key feature of the vilazodone clinical development program is the identification and development of biomarkers that predict response to therapy. This article will review the pharmacology, efficacy and tolerability, and pharmacogenetic data of vilazodone for the treatment of major depressive disorder. Vilazodone may be the first antidepressant to provide targeted therapy to patients most likely to achieve a response, and to offer an individualized approach to therapy.