Since release of the Institute of Medicine Report "To Err is Human:Building a Safer Health System" in 1999, a huge effort has been expended on error-related clinically applied research and on the implementation of new standards and practices related to quality improvement and patient safety. Nonetheless, measurable improvements in the quality of delivered care and reductions in medical errors have been variable and modest in most cases. Multiple barriers to the implementation of patient safety and error reduction initiatives have been identified in the literature. The greater part of this article is devoted to three fundamental barriers: physicians' intolerance for uncertainty, health professionals' fears, and an organizational structure and culture that are incongruent with increasing patient safety.