A dozen years ago, investigators identified adherence barriers to help guideline developers and other stakeholders design strategies to increase guideline use.1 Today, adherence to guidelines often remains low, causing omission of therapies recommended in the guidelines and contributing to preventable harm, suboptimal patient outcomes or experiences, or waste of resources. In part because of inadequate adherence to guidelines, preventable harm is the third leading cause of patient death, and one-third of health care spending—estimated at nearly $1 trillion, or $9000 per household—is for therapies that do not improve patients’ health.2 One estimate suggests that each year, 200 000 patients die from sepsis, 120 000 from teamwork failures, 100 000 from health care–acquired infections, 100 000 from venous thromboembolism and pulmonary embolus, 80 000 from diagnostic errors, and 68 000 from decubitus ulcers.3 Not all of these deaths are preventable, but many could be avoided if clinicians reliably used evidence-based therapies, many of which are included in guidelines. Increasing evidence suggests that harms once deemed inevitable, such as central line–associated bloodstream infections, are largely preventable. The Centers for Disease Control and Prevention (CDC) estimated that 100 000 to 200 000 fewer of these infections occurred in intensive care units (ICUs) between 1990 and 2010.4 One in five patients who develop these infections will die, and each infection costs approximately $40 000./.../5