Spinal cord injury is a catastrophic event that immeasurably alters activity and health. Depending on the level and severity of injury, functional and homeostatic decline of many body systems can be anticipated in a large segment of the paralyzed population. The level of physical inactivity and deconditioning imposed by SCI profoundly contrasts the preinjury state in which most individuals are relatively young and physically active. Involvement in sports, recreation, and therapeutic exercise is commonly restricted after SCI by loss of voluntary motor control, as well as autonomic dysfunction, altered fuel homeostasis, inefficient temperature regulation, and early-onset muscle fatigue. Participation in exercise activities also may require special adaptive equipment and, in some instances, the use of electrical current either with or without computerized control. Notwithstanding these limitations, considerable evidence supports the belief that recreational and therapeutic exercise improves the physical and emotional well-being of participants with SCI. This article will examine multisystem decline and the need for exercise after SCI. It will further examine how exercise might be used as a tool to enhance health by slowing multisystem medical complications unique to those with SCI. As imprudent exercise recommendations may pose avoidable risks of incipient disability, orthopedic deterioration, or pain, the special risks of exercise misuse in those with SCI will be discussed.