Abstract Restless legs syndrome (RLS) is a neurological disorder characterized by unpleasant sensations in the legs with an unknown etiology that affects as many as 65% of persons with multiple sclerosis (MS). There are currently no FDA approved treatments for RLS in persons with MS and the current pharmacological treatments are associated with a number of side effects, including the worsening of symptoms (i.e., augmentation). There further are no evidence-based behavioral approaches for managing RLS in persons with MS. Physical activity represents a promising, behavioral rehabilitation approach for managing symptoms of RLS in MS. To date, physical activity has demonstrated tremendous benefits for managing many consequences of MS, but there is no evidence on its efficacy for managing RLS in MS. This research proposes two methods for evaluating physical activity as an approach to manage symptoms of RLS in adults with MS and represents the first-step in establishing a research agenda that examines the efficacy of physical activity for inclusion in medical rehabilitation for managing RLS in MS. The first-step is a cross-sectional design that examines the relationship between physical activity behavior and RLS severity as it will describe the association in a large sample of individuals with MS and RLS. Those with RLS who engage in more physical activity (i.e., spend more time in light and moderate-to-vigorous physical activity) are expected to have a lower severity of RLS symptoms than those who spend less time physically active. The second-step involves a clinical trials experience within a randomized controlled trial and further permits an examination of the efficacy of physical activity for managing symptoms of RLS. This will be accomplished by directly comparing the effect of a six-month physical activity behavioral intervention with a control intervention on RLS severity. The hypothesis is that RLS symptom severity will be reduced for those who increase physical activity behavior as a result of the intervention. This project is vital to persons with MS, as it will be the first focal investigation of a possible behavioral intervention for managing RLS in MS. This project is a crucial first-step for informing future randomized controlled trials and designing larger-scale studies that can establish efficacy and effectiveness of physical activity for the management of RLS symptoms in persons with MS. This is consistent with the PI’s long-term interests in designing an appropriate behavioral rehabilitation approach to maximize the reduction of RLS symptoms and improve common correlates of RLS in neurological conditions.