With about 2.2 million Americans currently using wheeled mobility devices, wheelchairs are frequently provided to people with impaired mobility to provide accessibility to the community. Individuals with spinal cord injuries, arthritis, balance disorders, and other conditions or diseases are typical users of wheelchairs. However, secondary injuries and wheelchair-related accidents are risks introduced by wheelchairs. Research is underway to advance wheelchair design to prevent or accommodate secondary injuries related to propulsion and transfer biomechanics, while improving safe, functional performance and accessibility to the community. This paper summarizes research and development underway aimed at enhancing safety and optimizing wheelchair design.