Objective: To evaluate the safety of low doses of quetiapine when used for insomnia. Data Sources: A literature search was performed using PubMed and EMBASE (January 1990-November 2011) using the terms quetiapine, insomnia, sleep, low-dose, subtherapeutic, safety, and weight gain. Study Selection And Data Extraction:: Two prospective trials were identified that evaluated the effect of quetiapine in primary insomnia. In addition, 2 retrospective cohort studies were identified that evaluated the safety of low doses of quetiapine when used for Insomnia. Several case reports on adverse effects with low doses of the drug were also Included. Data Synthesis: Quetiapine is commonly used off-label for treatment of insomnia. When used for sleep, doses typically seen are less than the Food and Drug Administration-recommended dosage of 150-800 mg/day; those evaluated in the studies reviewed here were 25-200 mg/day). At recommended doses, atypical antipsychotics such as quetiapine are associated with metabolic adverse events (diabetes, obesity, hyperlipidemia). Adverse effects in the prospective trials were patient-reported and were minor, including drowsiness and dry mouth; however, tha trials were limited by their small sample size and short duration. The retrospective cohort studies found that quetiapine was associated with significant increases in weight compared to baseline. Serious adverse events identified from case reports included fatal hepatotoxicity, restless legs syndrome, akathisia, and weight gain. Conclusions: There are potential safety concerns when using low-dose quetiapine for treatment of insomnia. These concerns should be evaluated in further prospective studies. Based on limited data and potential safety concerns, use of low-dose quetiapine for insomnia is not recommended.