Loss of balance and walking ability are two of the primary impairments in multiple sclerosis (MS), which leads to loss of autonomy, increased fatigue perception, and disease severity in patients. Physical activity has been shown to ameliorate MS functional impairments, but there is limited evidence of synergistic efficacy of exercise training interventions that have both a resistance and aerobic focus in these patients. We evaluated the effect of a 12-wk combined training intervention (resistance and aerobic exercise) on balance, walking ability, fatigue perception, quality of life, and severity of disease in patients with MS. The combined training was well tolerated by the patients and improved the quality of life of the patients as also reflected in the improvement in walking and balance ability as well as reduced depression, fatigue, and severity of disease. The results of this study confirm the beneficial effects of physical activity in patients with MS and support the use of a combination of resistance and aerobic exercise training to achieve functional and psychological therapeutic outcomes.