Uncertainties concerning the pathology of multiple sclerosis have in the past led to numerous theories about the cause and therapy of the disease. In the last 40 years technological progress and the use of scientific research methods have contributed to a considerably enlarged body of medical and scientific knowledge, a process that has not yet come to an end. The attitude towards physical activity has also changed tremendously over time. There was a paradigm shift from the fear of triggering and aggravating the disease towards therapeutic benefits of physical activity and exercise. The first evidence for beneficial effects of exercise on symptoms and the course of the disease originated in the 1960s; however, a growing scientific interest in the topic was not recognizable until the 1990s when the number of exercise studies finally started to increase. Nowadays, the positive effects of physical activity and exercise are well established; nevertheless, high-quality research reports are still lacking. As a consequence there are still many unresolved questions concerning specific training effects and recommendations.