Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease characterized by the loss of upper and lower motor neurons. To date, no resolutive cure is available, and only two Food and Drug Administration-approved drugs are used to treat ALS without a resolutive outcome. In recent years, the study of the beneficial effects of physical activity on health has acquired special relevance. However, the relationship between ALS progression and physical exercise is still a hotly debated topic in medicine. Some studies have suggested higher risks to develop the disease that are associated with practicing intense physical activity, as seen in professional soccer or football players, for example. On the contrary, moderate training has been shown to exert several benefits in ALS-affected patients. Overall, more studies are needed to clarify whether physical activity is helpful or harmful for developing ALS.