The introduction of expensive disease-modifying agents for the treatment of multiple sclerosis (MS) has created the potential for patients with MS to become higher contributors to healthcare spending. In an attempt to make formulary and reimbursement choices for these agents, decision-makers may look to the literature for guidance. This critical review attempts to decipher a consistent message from the available economic literature regarding the relationship between disease severity and cost in MS. In the 2 studies that have examined MS disease severity, a positive correlation with total (direct and indirect) cost, indirect cost and some, if not all, components of direct cost was reported. In studies taking the societal perspective, the majority of total costs were indirect. This paper documents the high burden of MS on society and serves to guide the decision-maker in interpreting the MS economic literature such that this information can be optimally utilised to make informed resource allocation decisions.