The enzyme monoamine oxidase (MAO) has generated considerable interest as a biological marker. The serendipitous discovery that iproniazid was a weak MAO inhibitor (MAOI) led to the development and widespread use of MAOIs as antidepressants in the early 1950s. The-discovery of the two isoenzymes of MAO has led to the development of selective MAOIs that may have a more favorable side-effect profile. The regulation of MAO is multifactorial, and there is evidence that it involves estrogens. Improvement in mood and cognition reported in women on estrogen replacement therapy may also involve changes in MAO activity. The literature in this regard is reviewed here, and possible implications of the effects of estrogens on MAO activity are discussed.