People with a disability due to chronic illness or physical handicap exhibit pronounced physical inactivity. This is associated with an unfavorable lipid profile, peripheral insulin resistance with higher risk of diabetes mellitus type II, restriction of physical capacity and higher risk of coronary heart disease, especially in persons with spinal cord injury (SCI). Therefore, physical activity is important in rehabilitation and prevention, particularly in the handicapped. The data available show that comparable effects on cardiovascular and metabolic risk factors can be achieved in SCI patients, for example, as in non-disabled subjects. Positive effects are particularly attributed to endurance training with the goal of increasing daily activity and physical fitness. As in therapy with pharmaceuticals, the malfunctions attendant on the handicap, the kind, intensity, dosage, indications and contraindications of physical activity for SCI patients must be taken into consideration in prevention and rehabilitation and even beyond.