The use of monoamine oxidase inhibitors (MAOIs) in the treatment of depression has been bedeviled by reports of potentially dangerous or even fatal interactions with dietary amines and other drugs together with reports of more conventional toxicity to organs such as the liver. As a result, these otherwise very important and useful drugs have not been employed clinically as much as their effectiveness as antidepressants would indicate. Many of these unwanted actions were due partially or entirely to the fact that the older MAOIs all inhibited MAO irreversibly. The introduction of reversible inhibitors of monoamine oxidase-A (RIMAs) has greatly reduced both the number and severity of these interactions and, in particular, the risk of hypertensive crises following the ingestion of tyramine (the "cheese effect"). Potential interactions may remain with inhibitors of the uptake of 5-hydroxytryptamine, including pethidine and rapid release formulations of nasal decongestant amines. Potential interactions between RIMAs and other drugs that compete for the same metabolic pathways may still occur but should only result in changes in duration of action.