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Encouraging an active lifestyle is an essential part of successful rehabilitation programs, and the link between physical activity and quality of life (QOL) is well established among patients with mobility disorders. Biomechanical aspects of wheelchair design play an important role in physical activity and social participation of disabled individuals. This review focuses on key biomechanical features of wheeled mobility devices including propulsion methods, overuse injuries, assistive technologies, prevention of pressure ulcers, and tire and frame design. We briefly review the role of design modifications in increasing the physical activity and improvement of QOL among wheelchair-bound adults.