Natalizumab (Tyasabri((R))) is the first monoclonal antibody approved for use in relapsing-remitting multiple sclerosis. Based on indirect comparison, it seems more effective than alternative drugs in terms of reductions in disability progression, relapse rate and increase in quality of life during the initial 2 years of treatment. The annual direct drug cost of natalizumab is approximately euro25,500 compared with euro12,800-13,500 for alternative drugs, and the budgetary implications make it important to compare the health benefit and the cost of treatment. However, the long-term effect on disability and quality of life is uncertain, and neither the effect as second-line monotherapy nor the effect compared with alternative treatments has been established. The manufacturer has calculated cost per quality-adjusted life year to euro36,000-64,000 compared with alternative drugs and euro46,500-76,000 compared with best supportive care. Two studies comparing cost per relapse avoided with other drugs have reached conflicting results. Given the high socioeconomic burden of multiple sclerosis, natalizumab may be cost effective from a societal perspective, however, the models used to reach this conclusion rest on several uncertain assumptions.