Nearly fourteen years ago the Institute of Medicine’s report, To Err Is Human: Building a Safer Health System, triggered a national movement to improve patient safety. Despite the substantial and concentrated efforts that followed, quality and safety problems in health care continue to routinely result in harm to patients. Desired progress will not be achieved unless substantial changes are made to the way in which quality improvement is conducted. Alongside important efforts to eliminate preventable complications of care, there must also be an effort to seriously address the widespread overuse of health services. That overuse, which places patients at risk of harm and wastes resources at the same time, has been almost entirely left out of recent quality improvement endeavors. Newer and much more effective strategies and tools are needed to address the complex quality challenges confronting health care. Tools such as Lean, Six Sigma, and change management are proving highly effective in tackling problems as difficult as hand-off communication failures and patient falls. Finally, the organizational culture of most American hospitals and other health care organizations must change. To create a culture of safety, leaders must eliminate intimidating behaviors that suppress the reporting of errors and unsafe conditions. Leaders must also hold everyone accountable for adherence to safe practices.