The growth of health care simulation in schools of medicine and nursing is noteworthy, as is the increasingly sophisticated simulation technology, support from funding agencies and foundations for research, well-attended annual conferences, and continued interest of accreditation and certification groups. Yet there are concerns preventing the full value of health care simulation to be realized when examined from a patient safety perspective. Basic questions are asked by funders of patient safety research when assessing past simulation projects undertaken to advance patient safety: Are the safety and quality of care to patients actually improved, and is something new being learned regarding the optimal use of simulation? Concerns focus on pursuing the right research questions to learn something new about the most effective use of simulation; doing more with simulation than simply providing an interesting, stand-alone educational experience; attending more seriously to how skill acquisition, maintenance, and progression get managed; and encouraging investigators, funders, and reviewers to expand their vision regarding what constitutes important inquiry and evidence in health care simulation. Patient safety remains a multifaceted challenge in the United States, requiring multifaceted approaches. Simulation training is considered a promising approach for improving the safety and quality of health services delivery. While it takes time for any new approach to gain momentum and learn from past efforts, it also will require addressing a systematic range of essential questions to improve existing knowledge on the optimal use of simulation, and to realize similar gains in safety that other high-risk industries have made.