OBJECTIVES: The purposes of this article are to highlight the role of informatics in promoting patient safety and enabling evidence-based practice (EBP), 2 significant aspects for assuring healthcare quality; to delineate some challenges for the future; and to provide key recommendations for education, practice, policy, and research. METHODS: First, we describe the components of an informatics infrastructure for patient safety and evidence-based practice. Second, we address the role of informatics in 4 areas: 1) information access; 2) automated surveillance for real-time error detection and prevention; 3) communication among members of the healthcare team; and 4) standardization of practice patterns. Last, we delineate some future challenges for nursing and for informatics and provide key recommendations for education, practice, policy, and research. RESULTS: The components of an informatics infrastructure are available and applications that bring together these components to promote patient safety and enable EBP have demonstrated positive or promising results. CONCLUSIONS: Challenges must be addressed so that an informatics infrastructure and related applications that promote patient safety and enable EBP can be realized.