Systematic review is a means of reviewing clearly formulated questions by using an explicit methodology to minimize bias in the location, selection, critical evaluation, and synthesis of research evidence from existing studies. It is not enough, however, to simply know that the best evidence available was captured in a systematic review. Rather, health care decision makers also need to understand what the strength of that evidence is. Strong evidence of a therapy's benefits and harms facilitates sound judgment in clinical practice, compared with weak evidence. In the absence of an organized method, different clinicians may review the same data and differ on their impression of the strength of evidence but not understand why they differ. A wide variety of grading systems are available to rate the strength of evidence, but different organizations may weigh features or domains of these systems differently. Also, the published articles written on how to grade the strength of evidence are not likely to penetrate to the clinician's level and are not written so that practicing clinicians can understand them. In this article, we provide a better understanding of the key criteria or domains that should be considered when rating the strength of a body of evidence, why they are important, and the domains included in some of the validated and commonly used scales. This not only will enable clinicians and health care decision makers to personally grade the strength of evidence and be able to extend it to their clinical practices, but also will allow them to understand which domains are and which are not covered, and how different grading scales can provide different results and still be accurate based on the domains they include.