The neurotransmitter noradrenaline is known to be involved in a range of physiological and psychological processes, and dysfunctions of this neurotransmitter system have been implicated in a range of psychiatric disorders. However, the clinical utility of targeting the noradrenergic system in the treatment of such disorders has been somewhat overshadowed by the availability of agents selective for the serotonin system. A number of antidepressants with increased, but varying, selectivity for the noradrenergic system have become available in recent years, including mirtazapine, bupropion and, most recently, the first truly selective noradrenaline reuptake inhibitor, reboxetine. This review brings together current thinking on the role of noradrenaline in the aetiology and therapy of mood disorders to encourage a rational, evidence-based approach to the treatment of such disorders, and to provide suggestions and guidelines for future research in the area.