Metabolic abnormalities such as obesity, diabetes and dyslipidaemia increase the risk of cardiovascular disease, as well as a number of other adverse long-term health consequences. There is increasing evidence from case studies, retrospective analyses and clinical trials to suggest that second-generation antipsychotics can increase the risk of metabolic abnormalities in patients with schizophrenia, with indications that the level of risk may vary among antipsychotic medications. Comparison of weight gain data for the second-generation antipsychotics provides strong evidence to indicate differences in the weight gain liability, with clozapine and olanzapine being associated with the greatest weight gain over 1 year. Data suggest that these treatment-induced changes in weight are primarily responsible for treatment-related changes in glucose metabolism; however, there is also evidence to suggest that some impairments in glucose metabolism may be independent of adiposity. Studies investigating the effects of atypical antipsychotics on glucose metabolism have used a number of techniques of varying sensitivity and quality in an attempt to assign causality. Recent studies using gold standard methodologies, for both insulin sensitivity and adiposity, have shown that psychiatric patients receiving antipsychotics are at least as sensitive to the adverse effects of adiposity on glucose and lipid metabolism as non-psychiatric controls. This demonstrates the importance of weight gain prevention in psychiatry to help reduce long-term risk. There is also growing evidence to suggest that the differential effects of second-generation antipsychotics on metabolic parameters also result in differences in the risk of metabolic syndrome, with olanzapine having a significantly higher risk than either aripiprazole or ziprasidone. This differential risk highlights the need for adequate monitoring in patients receiving treatment with second-generation antipsychotics and careful selection of treatment in high-risk patients.