Case reports and case series are uncontrolled study designs with a high risk of bias but have significantly influenced medical literature and continue to advance medical knowledge. This guide presents a framework for evaluating, synthesizing, and applying evidence from case reports and case series. It proposes a tool to assess methodological quality based on four domains: selection, ascertainment, causality, and reporting. The tool includes signaling questions to aid evidence-based practitioners and systematic reviewers in their assessment. The guide also discusses the synthesis of case reports and case series, including narrative and quantitative synthesis methods. It emphasizes that while case reports and case series have low certainty of evidence, they can still inform decision-making when no higher-level evidence is available. The GRADE approach is recommended for rating the certainty of evidence and the strength of recommendations. The guide concludes that case reports and case series should be incorporated into decision-making when no other higher-level evidence is available, and that systematic reviews of case reports and case series should be conducted to facilitate their use in clinical practice.Case reports and case series are uncontrolled study designs with a high risk of bias but have significantly influenced medical literature and continue to advance medical knowledge. This guide presents a framework for evaluating, synthesizing, and applying evidence from case reports and case series. It proposes a tool to assess methodological quality based on four domains: selection, ascertainment, causality, and reporting. The tool includes signaling questions to aid evidence-based practitioners and systematic reviewers in their assessment. The guide also discusses the synthesis of case reports and case series, including narrative and quantitative synthesis methods. It emphasizes that while case reports and case series have low certainty of evidence, they can still inform decision-making when no higher-level evidence is available. The GRADE approach is recommended for rating the certainty of evidence and the strength of recommendations. The guide concludes that case reports and case series should be incorporated into decision-making when no other higher-level evidence is available, and that systematic reviews of case reports and case series should be conducted to facilitate their use in clinical practice.