The aim of this paper is to show how pertinent pathophysiological bases have been built for physical activity prescription for individuals with obstructive pulmonary disease (asthma and chronic obstructive pulmonary disease). The pathophysiological bases were constructed by taking into account exercise mismatching, which was analyzed in terms of both short- and long-term impact on disease outcome. Specific exercise adaptations based on a keen understanding of the underlying physiological processes provided the key to an adapted intervention with well-defined exercise program aims. The results that were achieved are striking, and one might conclude that sometimes exercise is simply the best way to improve the general well-being of individuals with chronic disease. Since this is a major concern for health professionals and chronically ill individuals, physical activity offers a means to rise to this challenge.