Prof. Robert Motl has systematically developed a research agenda that focuses on physical activity and its measurement, predictors, and consequences in persons with neurological diseases, particularly multiple sclerosis (MS). Prof. Motl has generated a body of research on the validity of common physical activity measures in persons with MS. This has resulted in foundational research on quantifying differences in physical activity, particularly rates of moderate-to-vigorous physical activity, in persons with MS. These two lines of research have provided the basis for examining the outcomes of physical activity in MS, particularly beneficial adaptations in brain structure, cognition, depression, fatigue, walking disability, and quality of life. Prof. Motl has undertaken research on social-cognitive predictors of physical activity that has informed the design of behavioral interventions for increasing physical activity in MS. This agenda serves as a test-bed for application and expansion into other conditions such as spinal cord injury and Parkinson’s disease.