Patient safety suddenly burst into public consciousness in the late 1990s and became a “celebrated” cause in the 2000s. It has since gradually faltered, and little improvement has been noted over almost 20 years. Both the rise and fall of patient safety demand explanation. Medical harm had been known long before the 1990s, so why did it suddenly become popular? And why were safety efforts ineffective? The authors propose that this rise was due to a discursive shift that reframed “medical harm” into “medical error” in the setting of anxiety about industrialization and great change in healthcare. The “error” framing, with its inherent notion of agency, was useful in advancing the agenda of a technocratic, managerial group of health professionals and diminishing the authority of the old guard based on clinical expertise. The fall was due to this “medicalization” of safety. Health professionals and managers with little knowledge of safety science came to dominate the patient safety field, crowding out expertise from the safety sciences (e.g., psychology, engineering) and thus keeping reform under the control of the healthcare establishment. Operating with a sort of delusional clarity, this scientific-bureaucratic cabal generated a great deal of activity but made little progress because they failed to engage with expertise in the safety sciences. Twenty years after sudden popularity, there is general agreement that little of value has been achieved. The future of patient safety is in doubt, and radical reform in approaches to safety will be required for progress to be made.