The Institute of Medicine report, To Err Is Human, marked the founding of the patient safety field. This special issue of Health Affairs, published 20 years after that report, highlights achievements and progress to date. One implementation study of evidence-based surgical safety checklists demonstrated that leadership involvement, intensive activities, and engagement of frontline staff are all critical to successful adoption of safety practices. Another study demonstrated that communication-and-resolution programs either decreased or did not affect malpractice costs, providing further support for implementing such programs. Experts describe the critical role of human factors engineering in patient safety and outline how to enhance the use of these methods. The concluding editorial by David Bates and Hardeep Singh points to progress in reducing hospital-acquired infections and improving medication safety in acute care settings and highlights remaining gaps in the areas of outpatient care, diagnostic errors, and electronic health record safety. In the related information, the Moore Foundation provides free access to five articles in this special issue.