Multiple sclerosis is a rare disease that affects the central nervous system, has a significant impact on health-related quality of life, and places a high financial burden on persons who have the disorder. Our Tier I project created an infrastructure allowing people with multiple sclerosis to discuss and prioritize research areas of greatest importance and connect with research and medical professionals with whom to collaborate. Our Tier II project supported the Patient-Led Multiple Sclerosis Community in becoming independent and selecting a comparative effectiveness research question. During Tier III we will develop a research proposal and apply for funding to answer the following question: Which exercise program is better for people with multiple sclerosis: treadmill, aquatic, or yoga? This is a process of developing a symbiotic relationship, with patients sharing their expertise and lived experience and researchers sharing their expertise and assessment of knowledge gaps. A literature synthesis committee will identify what we already know from prior research. During the first phase of the project, a search committee will collaborate with a variety of patients, researchers, and other stakeholders to develop the proposal committee. In March 2018, a patient and researcher will be identified as co-investigators to lead the proposal committee. Partners include Patient-Led Multiple Sclerosis Community, Illinois Neurological Institute, Central Illinois MS Council, Jump Simulation and Education Center, National Multiple Sclerosis Society, Exercise Neuroscience Research Laboratory University of Illinois Urbana Champaign, and Center for Outcomes Research and Department of Medicine at the University of Illinois College of Medicine Peoria.