Selegiline transdermal system (STS) has been approved to treat major depressive disorder in the USA. STS represents a novel generation of monoamine oxidase inhibitors with a superior safety profile to older monoamine oxidase inhibitors, in particular with regard to food interactions. The efficacy and safety of STS has been established in shortand long-term clinical trials. STS expands the range of pharmacological treatment options available to clinicians to treat major depressive disorder, in particular major depressive disorder with atypical features or treatment-resistant depression. This article discusses the mechanism of action of STS, summarizes efficacy and safety data from clinical trials, reviews drug and food interactions with STS and offers suggestions for use of STS in clinical practice.