Multiple sclerosis (MS) represents the second most common cause of neurological disability in young adults. The introduction of treatments that can change the natural course of the disease has focused attention on the economic burden of MS. There have been fears that the newly approved treatments for MS will ruin healthcare systems. Other published economic evaluations stress that the economic burden of a disease should be seen in a global perspective and that new treatments offer an opportunity to reduce the burden of the disease in the long-term. This paper reviews a number of key health economic studies in MS, which reveal the burden of MS on society and the cost-effectiveness of the new disease-modifying drugs, and highlight some unresolved issues. All relevant costs, including indirect costs and costs of informal care, should be taken into account for a global estimation of the cost/benefit balance. Further rigorous economic evaluations, focusing on the comparison of different available alternatives, are necessary. A major task will be the collection of data on the impact of the new disease-modifying therapies in reducing disability progression over the long-term, outside clinical trials. Gathering this kind of information is of critical importance in order to improve the precision of cost-effectiveness estimates in the future.