BACKGROUND: Recently, much attention has been focused on the increased rate of metabolic syndrome componen ts among psychiatric patients, including glucose intolerance, hyperglycemia, diabetes mellitus, hyperlipidemia, hypertension, and weight gain. Various reports have identified cases of newly diagnosed diabetes during treatment with atypical antipsychotic agents. However, the question remains whether there is a relationship between atypical antipsychotic use and the metabolic syndrome or whether there is a higher risk in this population irrespective of medication use. METHOD: Many articles on antipsychotics and metabolic issues are reviews of case reports or small, cross-sectional laboratory studies highlighting the suspected potential for differing rates of new-onset diabetes cases. We conducted a retrospective review of the literature from 1998 through 2002, using the MEDLINE database, and recent studies presented at major psychiatric medical conferences to create a broader perspective on the metabolic issues. RESULTS: We identified over 70 abstracts and published manuscripts, including case reports; cross-sectional lab studies; retrospective analyses of head-to-head, controlled clinical studies; retrospective database studies; pharmacoepidemiology studies; and prospective head-to-head studies presented in the past 4 years. Studies assessed differences in fasting plasma glucose, oral glucose tolerance tests (OGTT), modified OGTT, frequently sampled intravenous glucose tolerance tests, homeostasis model assessment-insulin resistance, odds or hazard ratios, prevalence, and incidence, as well as other elements of the metabolic syndrome. CONCLUSION: Data from this large body of scientific evidence indicate that the psychiatric patient population may be at a higher risk for the development of obesity, glucose homeostasis dysregulation, and hyperlipidemia compared with the general population. The available data do not demonstrate a consistent or clinically significant difference in the risk of new-onset diabetes during treatment with the various atypical antipsychotic agents.