More than half of US jurisdictions have laws criminalizing knowing exposure to or transmission of HIV, yet little evidence supports these laws' effectiveness in reducing HIV incidence. These laws may undermine prevention efforts outlined in the US National HIV/AIDS Strategy, in which the United States has invested substantial federal funds. Future research should include studies of (1) the impact of US HIV exposure laws on public health systems and practices; (2) enforcement of these laws, including arrests, prosecutions, convictions, and sentencing; (3) alternatives to HIV exposure laws; and (4) direct and opportunity costs of enforcement. Policy efforts to mitigate potential negative impacts of these laws could include developing prosecutorial guidelines, modernized statutes, and model public health policies and protocols.