Multiple sclerosis (MS) affects an estimated 400,000 people in the United States and results in a number of outcomes, including cognitive and motor dysfunction, symptoms of fatigue, pain and depression, comorbidity, and compromised quality of life. There is emerging evidence that restless legs syndrome (RLS) is another manifestation of MS, yet there is minimal research to date investigating safe and efficacious management of RLS within the MS population. This paper provides a broad overview of RLS, focuses on RLS in MS, and proposes an agenda for future research that includes rehabilitation as a non-pharmacological approach for the management of RLS in MS.