Serious mental illness (SMI) is defined generally as a major mental or behavioral disorder, causing substantial impairment in multiple areas of daily functioning. SMI affects about 4 to 8 percent of adults and includes disorders such as schizophrenia and bipolar disorder but not isolated substance abuse or developmental disorders. Individuals with SMI have shortened life expectancies relative to the general population to an extent that is not explained by suicide and accidents alone. This population experiences higher rates of morbidity from multiple general medical conditions, including diabetes and cardiovascular disease (CVD). Among patients using the public mental health system, heart disease was the leading cause of death. This excess of CVD-related mortality may be due to a number of factors, including direct effects of the illness, medications used to treat SMI, modifiable behavioral risk factors, and disparities in access and quality of health care. The review was designed to evaluate strategies to improve CVD risk factors in adults with SMI. SMI has been defined variously by different groups over time. For the purposes of this evidence review, people with SMI are defined as individuals who have: (1) schizophrenia or schizoaffective disorder (or other related primary psychotic disorder), (2) bipolar disorder, or (3) current major depression with psychotic features. We also included studies that enrolled adults with SMI or severe and persistent mental illness (SPMI) but did not specify diagnoses. The KQs considered in this comparative effectiveness review were: KQ 1: What is the effectiveness of weight-management behavioral interventions (e.g., behavioral counseling, health education), peer or family support interventions, pharmacological treatments (e.g., orlistat, topiramate), antipsychotic medication--switching to an antipsychotic with a low or neutral impact on weight, or their combination on weight control and related physical health outcomes (e.g., health-related quality of life, mortality) compared with each other or with usual care (or other control) among adults with serious mental illness (SMI) who are overweight, obese, or taking antipsychotics? KQ 2: What is the effectiveness of diabetes-management behavioral interventions (e.g., behavioral counseling, health education), peer or family support interventions, pharmacological treatments (e.g., rosiglitazone, metformin), antipsychotic medication-switching to an antipsychotic with a low or neutral impact on glucose level, or their combination on glucose level control and related physical health outcomes (e.g., health-related quality of life, mortality) compared with each other or with usual care (or other control) among adults with SMI who have diabetes or are taking antipsychotics? KQ 3: What is the effectiveness of dyslipidemia-management behavioral interventions (e.g., behavioral counseling, health education), peer or family support interventions, pharmacological treatments (e.g., statins), antipsychotic medication-switching to an antipsychotic with a low or neutral impact on lipid levels, or their combination on lipid-level control and related physical health outcomes (e.g., health-related quality of life, mortality) compared with each other or with usual care (or other control) among adults with SMI who have dyslipidemia or are taking antipsychotics? KQ 4: What is the effectiveness of multicondition lifestyle interventions (e.g., combinations of smoking cessation, physical activity, and nutrition counseling with or without medication management) on cardiovascular risk factors and related physical health outcomes (e.g., health related quality of life, mortality) among adults with SMI who have cardiovascular disease, elevated cardiovascular risk (e.g., hypertension), or are taking antipsychotics?