This commentary summarizes the work produced in Making Health Care Safer: A Critical Analysis of Patient Safety Practices, a report that detailed the evidence behind more than 80 safety practices. The same authors here discuss the efforts of the comprehensive and influential report in the context of how evidence-based principles can and should be applied to patient safety literature. The opinions shared explore the tension between relying on evidence for practices that make "common sense" versus those that carry significant opportunity costs in the absence of such evidence. This commentary was written as a point–counterpoint to a second commentary that focused on the limitations created by relying on evidence-based medicine in improving patient safety. The two articles together provide an excellent overview of the practical challenges that health care organizations face in making decisions about their patient safety programs, the associated costs, and the choices in potentially implementing one practice at the expense of another. The lead author of this commentary also wrote a perspective piece entitled "Interpreting the Patient Safety Literature" on AHRQ WebM&M.