Bupropion is an antidepressant thought to work through effects on norepinephrine and dopamine. It was first marketed in the USA in 1989 as a thrice-daily immediate-release preparation. This was followed in 1996 by twice-daily sustained-release and, most recently in 2003, by once-daily extended-release preparations. Its clinical efficacy for treating depression is equivalent to that of other antidepressants. In addition, the extended-release preparation has been shown to be effective for treating geriatric depression and depression characterized by reduced energy, pleasure and interest, and for preventing recurrence of seasonal affective disorder. Favorable aspects of its side-effect profile include low likelihood of somnolence, sexual dysfunction and weight gain. This review provides a history of the evolution of bupropion in its three formulations, with an emphasis on the efficacy and tolerability of the extended-release preparation.