OBJECTIVES: In considering the impact of Multiple Sclerosis (MS) and its treatment, evidence from other chronic conditions suggests that the economic burden is highly dependant on level of physical disability. We performed a comprehensive review of the economic literature to identify what is known about the relationship between EDSS categories and cost of MS. METHODS: The review of literature was a multi-step process - identification of databases, abstraction of individual articles and creating evidence tables. We sought cohort studies of patients with MS that describe costs attributed to each EDSS score, and utilized specific inclusion criteria for the selection of 10 studies. RESULTS: Both direct (medical) and indirect (productivity) costs rise continuously with increasing EDSS category, this rise is qualitatively exponential. The rise in indirect costs appears at lower EDSS scores. The cost of a relapse occurring in any given EDSS category exceeds that associated with that particular EDSS category. Few studies comprehensively assessed the entire spectrum of the costs associated with MS, and much of the literature is based on EDSS categories in a coarser grouping. The costs will depend on the practices that were current in the population under study, making this a moving target. CONCLUSION: As more expensive interventions become available, cost considerations - and cost-effectiveness analyses in particular - will become increasingly relevant to decision makers, requiring cost estimates that explicitly address the impact of progression of disability. This is a topic of sufficient importance to deserve more precise and detailed research.