Combinations of monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) are discussed with regard to general toxicity, drug interactions, animal studies, clinical reports, efficacy of combination therapy and usage conditions. Although MAOI-TCA combinations are usually considered contraindicated, informed opinion has shifted to cautious recommendation for the combination. Only refractory patients in whom less hazardous treatment has failed should be considered for combination therapy. The preferred dosage regimen is administration of the MAOI t.i.d. during the day and the entire TCA dose at bedtime. Patients should be informed of the immediate need for medical advice should side effects occur. It is concluded that the simultaneous administration of these agents is potentially efficacious and safe is carefully monitored and controlled.