Antidepressant activity of monoamine oxidase inhibitors (MAOIs) was initially noted in the 1950s, and by the early 1960s, they were a mainstay of antidepressant treatment. Reports of adverse events such as acute hypertensive reactions following the ingestion of certain foods and beverages tempered clinicians' enthusiasm for MAOIs. Introduction of the tricyclic antidepressants and the selective serotonin reuptake inhibitors led to declines in the use of MAOIs. However, MAOIs have been well established as an effective intervention for people with treatment-resistant depression, and transdermal formulations may provide a valuable therapeutic option and eliminate the drug-food interaction.