Individuals with serious mental illness (SMI) have shortened life expectancies relative to the general population to an extent that is not explained by unnatural causes such as suicide or accidents. Epidemiological studies have estimated the life expectancy of individuals with schizophrenia to be 10 to 25 years less than the general population. Increased morbidity of both chronic and acute illnesses in individuals with SMI also reduces quality of life and increases the overall burden of disability beyond that of the SMI itself. SMIs have an overwhelming economic impact, as measured by direct and indirect costs, including health care costs, disability payments, lost productivity, and law enforcement costs. For example, one study estimated annual costs due to schizophrenia to be $62.7 billion annually in the U.S., and patients with bipolar disorder are estimated to have the highest total health care costs of any mental illness with up to 70 percent of these costs in non-mental health (e.g., primary care) settings. Given these issues, methods to improve general medical services for individuals with SMI is a pressing priority. The issues that influence general medical outcomes for individuals with SMI are complex and overlapping and likely vary by disease state. Relevant factors can be categorized to include population characteristics, contextual and system factors, provider factors, and community resources. Interventions aimed at improving general medical outcomes in this population could be directed at any one, or several, of these factors. The populations of individuals with SMI have consistently shown higher rates of illnesses, such as infectious disease, diabetes, respiratory illness, and cardiovascular disease, than the general population. Modifiable risk factors for poor health, such as smoking, obesity, alcohol and substance abuse, and lack of exercise, are highly prevalent in individuals with SMI-as are obstacles to optimal health care such as poverty, homelessness, and social isolation. Multiple studies show diminished guideline concordance of general medical care provided to individuals with SMI, as evidenced by reduced receipt of preventive medical services and lower quality of chronic disease management for illnesses such as diabetes and cardiovascular disease as well as acute illnesses such as myocardial infarction. In addition, psychiatric medications can be risk factors for poor health given the association with some pharmacological treatments and medical outcomes such as increased risk of sudden death, hyperglycemia, hyperlipidemia, and weight gain. We conducted a systematic review of the peer-reviewed literature to answer the following key questions (KQs): KQ 1. What types of care models have been evaluated prospectively that integrate mental health care and primary medical care with the goal of improving general medical outcomes for individuals with serious mental illness (SMI)? KQ 2. Do models of integrated care for individuals with SMI improve the process of care for preventive services (e.g., colorectal cancer screening) and chronic disease management (e.g., annual eye examination in patients with diabetes mellitus DM])? KQ 3. (3a) Do models of integrated care for individuals with SMI improve general functional status outcomes (e.g., as measured by SF-36) or disease-specific functional status outcomes (e.g., Seattle Angina Questionnaire) related to medical care for chronic medical conditions such as DM, hypertension, or heart failure? (3b) Do models of integrated care for individuals with SMI improve clinical outcomes related to preventive services (e.g., influenza rates) and chronic medical care (e.g., kidney disease, amputations, retinopathy in patients with coexisting DM)? KQ 4. What are the gaps in evidence for determining how best to integrate care to improve general medical outcomes for individuals with SMI?