This review discusses the increasing demand for improving patient safety by presenting a framework for investigation. The authors begin with an overview of safety terms and the basics of safety and quality measurement while also sharing the challenges in choosing process versus outcome measures and tracking compliance with evidence-based guidelines. A number of case examples are provided to illustrate the various issues facing safety and quality researchers trying to apply the best tools. The discussion also includes the benefits and limitations of these measurement tools, including the Agency for Healthcare and Research Quality (AHRQ) Patient Safety Indicators. While the intensive care unit represents the contextual background for this review, a past study also discussed measurement strategies for patient safety more broadly.