Bupropion, a nor epinephrine and dopamine reuptake inhibitor, is approved for use in major depression and seasonal affective disorder and has demonstrated comparable efficacy in comparison to other antidepressants in clinical trials. Even after 20 years of introduction, bupropion has remained a safe and effective antidepressant, suitable for first-line use. There is increasing evidence that bupropion is one of the most widely selected agents and an effective augmenting agent for depressive patients with insufficient or partial response to serotonin re-uptake inhibitors. Several studies suggest that bupropion may offer a certain advantage over serotonergic antidepressants in the treatment of melancholic features of depression, including loss of pleasure, loss of interest, loss of energy and fatigue. The current review focuses on the therapeutic benefits of bupropion treatment in depressive patients in order to optimize its use in clinical practice.