Human immunodeficiency virus (HIV) infection meets many, if not all, of the established criteria that justify routine screening, and screening for HIV infection can be cost-effective depending on the population studied. In 2006, the Centers for Disease Control and Prevention recommended that HIV screening be included as part of routine care for most of the adult US population, but implementation of this policy has been slow. Mr Y is a 42-year-old man at relatively low risk of HIV infection who was offered testing by his primary care physician but declined it. He does not consider HIV infection to be a realistic possibility given his behavioral history and does not understand the purpose of being tested. The discussion that follows addresses the rationale for HIV screening, its potential benefits and risks, current testing options, and barriers to incorporating it into routine care.