Final evidence for the overall benefits of exercise therapy in the treatment/rehabilitation of specific chronic disease comes from randomized controlled trials (RCTs). This paper summarizes current evidence that is based on a systematic review including data from at least three RCTs with contrast for exercise only. The quality of specific RCTs as well as the quality of systematic reviews varies, the newest ones usually being of higher quality than the older ones. The most consistent finding of the studies is that aerobic capacity and muscular strength of patients can be improved without causing detrimental effects on disease progression. Severe complications during these carefully tailored programs were rare. The treatment periods and follow-up times of the majority of the RCTs are of a too short duration to document group differences in disease progression. However, exercise reduces disease-related symptoms in many diseases, such as osteoarthritis, asthma and chronic obstructive pulmonary disorder. Also, RCTs studying patients with coronary heart disease as well as patients with heart failure show that all-cause mortality is lower in exercisers than in controls.