Screening for presymptomatic disease provides the potential for early intervention and improved outcomes. However, although this practice has potential benefits, it also has potential harms that must be considered. The U.S. Preventive Services Task Force (USPSTF) is a nonfederal panel of experts convened by the Agency for Health Research and Policy to systematically review the evidence for preventive services, including disease screening, and to create evidence-based recommendations for primary care practice in the United States. As rheumatologists contemplate the potential of screening for preclinical disease, understanding the process used by the USPSTF can help guide research efforts supporting such screening.