Sedentary behavior is prominent in persons with multiple sclerosis (MS) and may be associated with negative health consequences, yet our knowledge of sedentary behavior and its measurement, correlates, and consequences is in a stage of infancy—the focus on behavioral interventions might even be premature. This underscores the need for a research agenda focusing on sedentary behavior and its measurement, correlates, and consequences to inform the design of targeted interventions for persons with MS. Such research is important, as sedentary behavior represents a large opportunity for focal, theory-based behavioral interventions that could not only decrease sedentary behavior but also provide consequential life-changing benefits for persons with MS. The time is ripe for focal inquiry on sedentary behavior in MS and pursuing a new paradigm on health behavior change in this population.