Throughout their careers, physicians are exposed to a wide array of assessments, including those aimed at evaluating knowledge, clinical skills, and clinical decision-making. While many of these assessments are used as part of formative evaluation activities, others are employed to establish competence and, as a byproduct, to promote patient safety. In the past 10 years, simulations have been successfully incorporated in a number of high-stakes physician certification and licensure exams. In developing these simulation-based assessments, testing organizations were able to promote novel test administration protocols, build enhanced assessment rubrics, advance sophisticated scoring and equating algorithms, and promote innovative standard-setting methods. Moreover, numerous studies have been conducted to identify potential threats to the validity of test score interpretations. As simulation technology expands and new simulators are invented, this groundbreaking work can serve as a basis for organizations to build or expand their summative assessment activities. Although there will continue to be logistical and psychometric problems, many of which will be specialty- or simulator-specific, past experience with performance-based assessments suggests that most challenges can be addressed through focused research. Simulation, whether it involves standardized patients (SPs), computerized case management scenarios, part-task trainers, electromechanical mannequins, or a combination of these methods, holds great promise for high-stakes assessment.