This commentary, written by leadership from the Agency for Healthcare and Research Quality (AHRQ) and the Centers for Medicare and Medicaid Services (CMS), shares the vision of how patient safety will be achieved through targeted federal initiatives. The authors discuss the shifting paradigm that must result in the way our health systems understand, learn from, and prevent errors. They discuss several strategies already in place to support the mission of their respective agencies "to support research, information, and partnerships to ensure that all Americans receive high-quality, safe, and efficient health care."