Monoamine oxidase (MAO) inhibitors (MAOIs) provide effective alternative therapy for those patients with major depression who do not respond to tricyclic antidepressants or such related compounds as the selective serotonin reuptake inhibitors. This article reviews studies on the efficacy of both the classical MAOIs and the new, selective monoamine oxidase-A (MAO-A) inhibitor brofaromine in patients with resistant major depression. Brofaromine appears to be as effective as the older MAOIs in these patients, but is better tolerated and safer to use. Brofaromine was also found to be better tolerated than lithium when added to treatment with the tetracyclic antidepressant maprotiline. More studies on the benefits of the new MAO-A inhibitors in resistant depression are indicated, not only with brofaromine but also with moclobemide, which to date has not been studied in this indication. Studies to determine their place in the overall treatment strategy of major depression are also needed.