OBJECTIVE To examine the efficacy of tasimelteon for the treatment of non-24-hour sleep-wake disorder using evidence from controlled clinical trials. DATA SOURCES Citations in Google Scholar and PubMed from January 1, 2008, to May 31, 2014, were identified using tasimelteon as the search term. STUDY SELECTION AND DATA EXTRACTION Results were limited to human trials published in English. Trials that compared tasimelteon with placebo were included. DATA SYNTHESIS A phase II trial (n = 39) evaluated the effects of tasimelteon versus placebo on improvements in sleep efficiency and the ability to shift circadian rhythms over 3 days. Significant shifts in circadian rhythm were only observed for 100-mg tasimelteon. A phase III trial (n = 412) evaluated the effects of tasimelteon versus placebo on assessment of latency to persistent sleep and wake after sleep onset; significant advantages were observed in tasimelteon recipients. The SET (Safety and Efficacy of Tasimelteon) trial (n = 84) enrolled blind men and women with Non-24. They received placebo or tasimelteon 20 mg daily. Tasimelteon recipients had significantly (P = 0.0025) better entrainment and N24CRS scores. The RESET (Randomized Withdrawal Study of the Efficacy and Safety of Tasimelteon) trial (n = 20) enrolled entrained participants from the SET trial who received 20 mg of tasimelteon or placebo daily for 8 weeks. The primary objective was to evaluate the maintenance of effect of tasimelteon to entrain circadian rhythms. Tasimelteon was associated with significantly (P = 0.0055) greater entrainment than placebo. CONCLUSION Tasimelteon improves sleep initiation and maintenance in patients with Non-24 who have a shift in endogenous circadian rhythms. However, the cost of this agent limits its use.