BACKGROUND: Physical activity may be neuroprotective in multiple sclerosis (MS). One review (2011) of exercise and MS disability was inconclusive, but highlighted the need for more studies. OBJECTIVE: To perform an updated systematic literature review examining the relationship between physical activity and physical ability outcomes in persons with MS. METHODS: EMBASE and MEDLINE were searched for original interventional studies (2011-2016) evaluating exercise on quantitative outcomes of physical disability in MS. We also assessed any reported adverse outcomes. RESULTS: Of the 153 articles identified, 12 were included; 3 examined endurance training; 6 resistance training; and 3 explored less conventional exercises, specifically, tai chi, kickboxing, and vestibular rehabilitation, each lasting 5-24 weeks. In total, 568 unique individuals were included, and >10 different scales used to assess outcomes. Endurance training provided benefits in walking ability, while mindfulness exercises (tai chi and vestibular rehabilitation), and dynamic workouts (kickboxing) led to improvements in balance and coordination. Resistance training alone did not improve walking ability, but improved lower limb muscular strength and endurance. When resistance and endurance training were combined, improvements were seen in mobility, balance and coordination. Four studies assessed discontinuation; most reported a return to pre-intervention function. Adverse outcomes were reported in 6 studies, and appeared generally mild, ranging from mild muscle soreness to exacerbation of MS symptoms. CONCLUSIONS: Physical activity was associated with measurable benefits on ability outcomes, but continuation is likely required to maintain benefits. While adverse events were generally mild, approximately half of studies actually reported safety outcomes.