OBJECTIVE: The authors critically reviewed the literature on clinical applications of sleep deprivation in the treatment of depression. DATA COLLECTION: They included all studies using sleep deprivation for clinical purposes, with the exception of treatment studies that did not provide follow-up beyond a night of recovery sleep. They focused on six uses of sleep deprivation: 1) to potentiate response to antidepressant medication (13 studies), 2) to hasten the onset of action of antidepressant medication or lithium (five studies), 3) to prevent recurrent mood cycles (four studies), 4) as an alternative to antidepressant medication (five studies), 5) as a diagnostic probe (two studies), and 6) to predict response to antidepressant medication (nine studies). FINDINGS: Although the literature appears to demonstrate the efficacy of sleep deprivation as a potentiation strategy, these treatment studies have substantial methodological shortcomings. Well- designed pilot studies indicate that sleep deprivation may hasten the onset of action of thymoleptic medications. Sleep deprivation may prevent premenstrual mood swings, and response to sleep deprivation may differentiate depressive pseudodementia from primary degenerative dementia with depression. Studies attempting to use sleep deprivation to predict response to antidepressant medication have yielded inconsistent results. CONCLUSIONS: Given the noninvasive nature of sleep deprivation, it would be useful to determine if even a small subset of refractory patients respond to it. The authors suggest future research directions to determine the usefulness of this potential treatment.Abstract Teaser