Critically ill infants are among the most medically fragile patients in hospitals today. Given their size and gestational age, the tolerance for error within this population is extremely small. Medical errors that may seem inconsequential in adults can have disastrous consequences for infants. This article describes one unit's experience with adverse patient events, and the resulting safety program that was developed to enhance the unit's safety culture. Specific strategies for successfully implementing a staff-focused patient safety program are provided. These strategies include the development of a unit-based interdisciplinary safety team to identify and respond to areas of risk; tools and techniques utilized for the analysis and prioritization of risk; incorporation of safety rounds as a means improving the safety culture; and implementation of staff-driven solutions to address safety concerns. The important role that parents and families can play in risk assessment and mitigation is reviewed, and the concept of parent partnerships is presented. Finally, initial program outcomes are discussed, and implications for other providers are suggested.