Healthcare providers have a basic responsibility to protect patients from accidental harm. At the institutional level, creating safe healthcare organizations necessitates a systematic approach. Effective use of informatics to enhance safety requires the establishment and use of standards for concept definitions and for data exchange, development of acceptable models for knowledge representation, incentives for adoption of electronic health records, support for adverse event detection and reporting, and greater investment in research at the intersection of informatics and patient safety. Leading organizations have demonstrated that healthcare informatics approaches can improve safety. Nevertheless, significant obstacles today limit optimal application of health informatics to safety within most provider environments. The authors offer a series of recommendations for addressing these challenges. This position paper focuses on next steps in using health informatics to improve patient safety. The paper does not attempt to provide a comprehensive review of patient safety-related technical accomplishments, because recent Institute of Medicine reports have done so. This paper focuses instead on current pressing issues and opportunities for addressing them in the short-term future. The intended audience includes provider organizations responsible for the safe delivery of health care; policy makers responsible for funding and regulatory decisions that influence healthcare safety; and the health informatics developers community (including vendors), who build the computer systems that support patient care.