Persons with hereditary neuromuscular diseases generally lead a sedentary lifestyle, placing them at risk for diseases associated with inactivity and causing weakness, which compounds their primary disease. Although research is lacking in this area, evidence to date suggests that this population may benefit from both strengthening and aerobic fitness training programs. Overwork weakness has not been demonstrated in controlled trials of exercise, but clinicians need to be prudent in their recommendations, encouraging alternating periods of physical activity with scheduled rest. Future investigations should focus on the primary symptom of fatigue, and quantify changes in the ability to work and participate in physical activities as outcome measures of an exercise program.