Creating safe passage for patients is a priority in hospitals across the United States, a priority in which critical care and advanced practice nurses play a crucial role. Three unique but related areas within this safety framework are fall prevention, the emerging practice of early mobility in intensive care, and safe patient handling. This article explores these 3 topics in tandem to determine whether sufficient evidence exists to guide fall prevention strategies, to explore patient safety associated with early mobility in intensive care units, and, because mobilizing patients is physically demanding for health care workers, to describe safe patient-handling techniques aimed at injury prevention for critical care nurses and others. A review of what is currently known about falls, effects of mobility, and safe patient handling provides a foundation for practice considerations and reveals research opportunities.