Medicine, as an industry in which human lives depend on the skill and performance of operators, must create and maintain a culture of safety, in addition to promoting the design of systems to mitigate errors. The use of medical simulation as a mechanism for training healthcare professionals in a safe environment is expanding rapidly. An important component of systems that ensure the safety of patients in the hospital setting is the interface between humans and technology in the hospital. The objective of this paper is to review: (1) the definition and a brief history of medical simulation, (2) examples of how current medical simulation centers are using simulation to address patient safety, and (3) examples of how simulation can be used to enhance patient safety through improvement of the interface between healthcare practitioners and medical technology. Medical simulation and human factors engineering can be used to examine and enhance the interface between healthcare practitioners and medical technology, with the potential to make a significant contribution to patient safety.