Elucidation of the mechanism of action of antidepressants led to the hypothesis that depression is caused by dysfunction in either the noradrenergic or serotonergic neurotransmitter systems. As inconsistencies in studies designed to conยฎrm this hypothesis arose, the consensus on the biological basis of depression is being reยฎned. The need for better tolerated and eective antidepressants has resulted in the development of agents with more speciยฎc receptor binding proยฎles than the tricyclic antidepressants. These newer antidepressants selectively inhibit the reuptake of noradrenaline (selective NARIs), serotonin (SSRIs) or both (SNRIs). They are useful tools for describing changes in neuroreceptors and intracellular events that occur during antidepressant pharmacotherapy. Reboxetine, a selective NARI, down-regulates b-adrenergic receptors and desensitises noradrenaline-coupled adenylate cyclase. It also aects cAMP-and Ca 2 /calmodulin-dependent phosphorylation systems in a dierent manner to tricyclic antidepressants and SSRIs. This implies that although dierent classes of antidepressants may aect common central pathways, the ways in which they do this are distinctive. In conclusion, reboxetine, a selective NARI which is well tolerated and eective in the treatment of depression, has provided us with a new insight into the action of antidepressants and thus will help us to reยฎne our theory of the biological basis of depression.