Hand hygiene has been recognized as the most important means of preventing the transmission of infection, and great emphasis has been placed on ways to improve hand hygiene compliance by health care workers (HCWs). Despite increasing evidence that patients’ flora and the hospital environment are the primary source of many infections, little effort has been directed toward involving patients in their own hand hygiene. Most previous work involving patients has included patients as monitors or auditors of hand hygiene practices by their HCWs. This article reviews the evidence on the benefits of including patients more directly in hand hygiene initiatives, and uses the framework of patient-centered safety initiatives to provide recommendations for the timing and implementation of patient hand hygiene protocols. It also addresses key areas for further research, practice guideline development, and implications for training of HCWs.