Although the selective serotonin reuptake inhibitors have become the first line medications for the treatment of depression, drugs primarily targeting the norepinephrine (NE) and/or the dopamine catecholaminergic systems are also effective. These include selective NE reuptake inhibitors, such as desipramine and reboxetine, the NE releaser bupropion and the α2-adrenergic antagonists mianserin and mirtazapine. Dopamine type 2 agonists are also effective in treating depression, although they are rarely used. Since the NE, dopamine and serotonin systems have reciprocal interactions, it is virtually impossible to act on a specific neuronal element without affecting in a cascade effect the two other systems. In this review, the primary actions of the catecholaminergic strategies upon their acute and long-term administration are described, as well as their impact on other systems. Their use in treatment-resistant depressed patients is also addressed.