Patients with schizophrenia are at significantly increased risk for infection with human immunodeficiency virus (HIV), hepatitis C virus, or both. Several factors underlie this increased risk, including substance abuse and high-risk sexual behavior. Although being sexually active tends to be less common among patients with schizophrenia than among nonpsychotic individuals, patients with schizophrenia who are sexually active are more likely than nonpsychotic individuals to engage in high-risk behavior. Many patients with schizophrenia have inadequate knowledge about the risks of HIV, but delivering factual information is not likely, by itself, to bring about behavioral changes that reduce the risk of exposure and transmission. Comorbidity of schizophrenia and life-threatening viral illnesses incurs a worse prognosis for both conditions. Nevertheless, effective pharmacotherapy exists, and antipsychotics and highly active antiretroviral treatments for HIV can be used together successfully. The clinical challenge is to encourage adherence to treatment and to coordinate the clinical services needed to address the diverse psychiatric and medical problems that coexist in this population.