Monoamine oxidase inhibitors (MAOIs) are infrequently used in the treatment of depression and anxiety disorders. Treatment guidelines consider them as 2nd to 4th line agents. This is largely the result of their well-known potential for interactions with dietary tyramine or sympathomimetics resulting in hypertensive reactions, with serotonergic agents resulting in serotonin syndrome, and the perception that these agents are poorly tolerated. MAOIs appear to be more effective than tricyclic antidepressants in the treatment of depression with atypical features. Four irreversible MAOIs are available in the United States: tranylcypromine, isocarboxazid, phenelzine, and transdermal selegiline; transdermal selegiline selectively inhibits monoamine oxidase B and may be less likely to interact with dietary tyramine and sympathomimetics. Moclobemide, a reversible, selective inhibitor of monoamine oxidase A is available in Canada, Europe and Australia; moclobemide’s interactions with dietary tyramine and sympathomimetics may be less troublesome because its inhibition is reversible. Food handling and storage processes have changed significantly since MAOIs were first introduced. As a result, significant amounts of tyramine are not as commonly found in most foods and beverages; dietary restrictions for patients taking MAOIs are less severe than in the past. MAOIs should not be co-administered with serotonergic agents as the combination creates a significant risk of serotonin syndrome. Adverse effects which may be encountered with MAOI treatment include transient hypertensive reactions, orthostatic hypotension, pyridoxine (vitamin B6) deficiency (phenelzine and possibly isocarboxazid), sexual dysfunction (mostly with phenelzine), sleep disturbances, rare hepatotoxicity (phenelzine), and weight gain (phenelzine). Significant discontinuation syndromes may be seen with isocarboxazid, phenelzine, and tranylcypromine. Tranylcypromine abuse may occur. MAOIs probably do not need to be discontinued prior surgery; there appears to be little risk of interactions between MAOIs and either general or local anesthetics. MAOIs have been safely used in patients undergoing ECT. MAOI overdoses are potentially life-threatening.