The U.S. Preventive Services Task Force (USPSTF) formulates evidence-based recommendations for clinical preventive services. These recommendations are communicated by letter grades that reflect the quality of evidence and the magnitude of net health benefit expected from delivering the preventive service. When the USPSTF finds insufficient evidence to determine the balance of health benefits or harms of delivering a preventive service, because of a lack of studies, poor-quality studies, or good-quality studies with conflicting results, the USPSTF assigns the service an I letter grade. The USPSTF found insufficient evidence to recommend for or against screening for hepatitis C virus infection in high-risk individuals (I letter grade). This recommendation reflects the need for further research that would provide adequate evidence to assess the net health benefit for persons screened for hepatitis C virus infection.