The United States leads the world in incarceration, which disproportionately affects disadvantaged individuals, including those who are mentally ill, poor, homeless and racial minorities. Incarceration is disruptive to families and communities and contributes to health disparities in sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). The objective of this grand rounds is to review (1) the epidemiology of incarceration in the United States, (2) the social factors which contribute to high rates of STIs in incarcerated individuals and (3) the HIV care cascade in incarcerated and recently released individuals. Routine screening and treatment for STIs and HIV in the criminal justice system can identify many new infections and has the potential to both improve individual outcomes and reduce transmission to others. Increased collaboration between the department of health and department of corrections, as well as partnerships between academic institutions and the criminal justice system, have the potential to improve outcomes in this vulnerable population.