Systematic reviews are essential to produce trustworthy guidelines. To assess the body of evidence included in a systematic review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group has developed an approach that is used by over 100 organizations, including the World Health Organization and Cochrane. GRADE provides operational definitions and instructions to rate the certainty of the evidence for each outcome in a review as high, moderate, low, or very low for interventions, prognostic questions, values and preferences, test accuracy, and resource utilization. GRADE includes assessing risk of bias, imprecision, inconsistency, indirectness, and publication bias, the magnitude of effects, dose–response relations, and the impact of residual confounding and bias. Assessments are presented in GRADE tables, which may be produced using the GRADEpro software tool. Guideline panels can use these tables to produce recommendations based on the GRADE Evidence to Decision frameworks.