This commentary discusses the concept of "sensemaking" as a mechanism to better understand and mitigate the factors that contribute to medical errors. The authors begin by presenting a conceptual framework of sensemaking before discussing both retrospective (eg, root cause analysis) and prospective (eg, failure mode and effect analysis) tools that can be employed within organizations. After discussing probabilistic risk assessment, a case example is provided to illustrate the use of these tools and what is learned from their collective findings. The authors conclude that identifying risks to patient safety represents a critical step in prevention through the design of targeted interventions.