Objectives: Depressed patients often have insomnia, daytime sleepiness, and/or changes in sleep architecture. These sleep/wake changes are associated with diminished quality of life, impaired function, diminished treatment response and greater risk of relapse. Antidepressants may cause, exacerbate, or ameliorate these sleep/wake alterations. The sleep/wake effects of bupropion, a norepinephrine/ dopamine reuptake inhibitor (NDRI), are relatively less well established. We carried out this literature review in order to characterize the sleep/wake effects of bupropion, provide an understanding of the antidepressant mechanisms involved and discuss implications for clinical practice. Methods: Manuscripts were identified using PubMed. In addition, reports were selected from references in the original search and reports concerning bupropion extended-release were provided by the manufacturer. Results: Bupropion was not associated with daytime sedation. Sleep disturbance occurs at a low rate, comparable to other modern reuptake inhibitors. Unlike other antidepressants, bupropion does not suppress REM sleep nor increase the risk of periodic leg movement disorder. Conclusion: Bupropion has a unique sleep/wake profile, which may be particularly well-suited for treatment of individuals suffering from depression accompanied by significant fatigue/sleepiness. A lack of REM suppression, which likely reflects bupropions NDRI mechanism of action, is also distinctive and does not affect antidepressant efficacy.