Vortioxetine is an orally administered small molecule developed by Lundbeck A/S for the once-daily treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Vortioxetine received its first global approval for MDD in the USA in September 2013 and regulatory approval for its use in this indication in the EU (where it has received a positive opinion) and Canada is awaited. The drug is a bis-aryl-sulphanyl amine compound that combines serotonin (5-HT) reuptake inhibition with other characteristics, including receptor activity modulation. In vitro studies indicate that vortioxetine is an inhibitor of the 5-HT transporter and is a 5-HT1D, 5-HT3 and 5-HT7 receptor antagonist, a 5-HT1A receptor agonist and a 5-HT1B receptor partial agonist. Animal and in vitro studies indicate that several neurotransmitter systems may be impacted by vortioxetine, with the drug enhancing levels of 5-HT, noradrenaline, dopamine, acetylcholine and histamine in certain areas of the brain, as well as modulating γ-aminobutyric acid and glutamate neurotransmission. Phase III trials of vortioxetine in both MDD and GAD have been conducted worldwide. This article summarizes the milestones in the development of vortioxetine leading to this first approval for MDD.