Monoamine oxidase (MAO) inhibitors (MAOIs) available at present can be classified into 3 types: (i) older, irreversible nonselective (first generation) agents such as phenelzine, tranylcypromine and isocarboxazid; (ii) irreversible, selective drugs (second generation) such as selegiline (deprenyl); and (iii) the new, third generation of reversible, selective MAO-A inhibitors such as moclobemide, toloxatone and brofaromine. This latter group of drugs are also known as RIMAs (reversible inhibitors of MAO-A). Although the clinical efficacy of MAOIs has been well documented in recent years, this class of antidepressants has, to date, played a subordinate therapeutic role in comparison with monoamine reuptake inhibitors, e.g. tri- and tetracyclic antidepressants and serotonin (5-hydroxytryptamine; 5-HT)-selective substances. The main reason for this is the risk of a hypertensive crisis arising from interactions with MAOIs and certain foods or drugs. However, the limiting safety problems of traditional MAOIs appear to have been overcome with the development of the RIMAs. Controlled trials against placebo and established antidepressants indicate that moclobemide and brofaromine are effective treatments for depression. The agents seem to be as effective as tranylcypromine and phenelzine. Selegiline has significant antidepressive efficacy, but only at high dosages where there is likely to be a loss of selective inhibition of MAO-B. Moclobemide has a more favourable overall tolerability profile than tranylcypromine, with a lower incidence of adverse effects. In particular, the lack of behavioural toxicity, minimal potentiation for the tyramine pressor response and safety in overdose are clearcut advantages of RIMAs over older MAOIs. In the light of existing clinical data, RIMAs such as moclobemide may become part of the renaissance of MAOIs in the treatment of affective disorders. The RIMAs, because of their favourable adverse effect, interaction and toxicity profiles can be considered as the first-line MAOIs. They can be used with minimal compliance-limiting dietary restrictions. However, in cases of nonresponsiveness or loss of efficacy the older, irreversible MAOIs still have a place in therapy, but only if patient and doctor compliance can be established. As far as long term and prophylactic treatment is concerned, the place of the newer MAOIs has still to be verified.