&NA;Recent studies have shown that monoamine oxidase inhibitors (MAOIs), in appropriate patients and with proper precautions, are not as dangerous as once thought, especially in comparison to alternative antidepressants. We review the literature regarding the combined use of MAOIs and tricyclic antidepressants, which has been reported to be both highly toxic and highly effective. A large number of reports of adverse effects and their management, uncontrolled clinical trials, and animal studies are summarized. We also discuss the three controlled studies of combined MAOI‐tricyclic therapy that have been undertaken. We conclude that the hazards of combination therapy have been exaggerated and that MAOI‐tricyclic therapy is a reasonable approach in patients found resistant to standard antidepressant treatment if certain precautions are observed.