Monoamine oxidase inhibitors (MAOIs) currently have a "bad rap" and are thus infrequently used in psychopharmacology, even by experienced clinicians. Misinformation about the dietary and drug interactions of MAOIs is widespread, whereas pragmatic tips for utilizing MAOIs to minimize risks and to maximize therapeutic actions are largely lacking in the contemporary literature. While clearly not first-line treatments, MAOIs, in the hands of experienced and well-informed clinicians, can be a powerful therapeutic intervention for patients with depression, panic disorder, and other anxiety disorders who have failed first-line treatments. This article focuses on the pharmacologic mechanisms of MAOIs, since an understanding of these mechanisms may provide a rationale to empower experts to expand their use of these agents. Discussed here are not only the mechanisms of therapeutic action of MAOIs, but also the mechanisms explaining their side effects, including hypertensive interactions with dietary tyramine (so-called "cheese reactions") and drug interactions that can lead to hypertensive reactions with some drugs and serotonin toxicities with others. This article also provides practical tips on how to use MAOIs, including debunking certain myths and giving specific guidance about which foods and drugs to avoid. Those with no previous interest in MAOIs may discover in this article a new "secret weapon" to add to their therapeutic armamentarium for patients who fail to respond to the better-known agents.