Objective: To review the published literature to evaluate the safety of overnight orthokeratology (OOK) for the treatment of myopia. Methods: Repeated searches of peer-reviewed literature were conducted in PubMed (limited to the English language) and the Cochrane Central Register of Controlled Trials (no language limitations) for 2005, 2006, and 2007. The searches yielded 495 citations. The panel reviewed the abstracts of these articles and selected 79 articles of possible clinical relevance for review. Of these 79 full-text articles, 75 were determined to be relevant to the assessment objective. Results: No studies were rated as having level I evidence. Two premarket applications to the Food and Drug Administration were rated as having level II evidence. There were 2 studies rated as having level II evidence. The main source of reports of adverse events associated with OOK was 38 case reports or noncomparative case series (level III evidence). Conclusions: The prevalence and incidence of complications associated with OOK have not been determined. Complications, including more than 100 cases of infectious keratitis resulting from gram-positive and gram-negative bacteria and Acanthamoeba, have been described in case reports and case series representing observations in undefined populations of OOK users. Data collection was nonstandard. Risk factors for various complications cannot be determined. Because OOK puts patients at risk for vision-threatening complications they may not encounter otherwise, sufficiently large well-designed cohort or randomized controlled studies are needed to provide a more reliable measure of the risks of treatment and to identify risk factors for complications. Overnight orthokeratology for slowing the progression of myopia in children also needs well-designed and properly conducted controlled trials to investigate efficacy. Because of variations in orthokeratology practice, a wide margin of safety should be built into OOK regimens. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.