The irreversible inhibitor of monoamine oxidase, tranylcypromine, is a potent antidepressant, but its use is limited to special indications due to side effects and dietary restrictions. The antidepressant action of tranylcypromine is not completely explainable by its effects on monoamine oxidase. Tranylcypromine also leads to an increase in brain trace amines, which are believed to play a key role in the pathophysiology of depression. It also affects other pathophysiological pathways associated with depression. Tranylcypromine treatment leads to an up-regulation of GABA(B)-receptors and modulates the phospholipid metabolism, which is essential for normal brain function. These findings implicate that the efficacy of tranylcypromine as an antidepressant may be due to its multiple actions within the human brain.