The growing number of disease-modifying treatments (DMTs) for patients with multiple sclerosis (MS) and the high acquisition costs of these DMTs are likely to increase the demand for information on their cost effectiveness. To improve the comparability and applicability of the findings from future cost-effectiveness analyses, it would be useful to have a clear understanding of the methodological challenges of modelling the cost effectiveness of DMTs in MS and the different approaches taken by such studies to date. In contrast to previous review studies, this review focuses on long-term time horizon (≥10 years) simulation-based cost-effectiveness analyses with homogeneous contexts of analysis (i.e. those with similar study objectives, comparators, and target populations) published over the past decade. By doing so, it provides a clearer picture of how modelling approaches taken in the existing studies truly differ across studies, and reveals major areas for improvement in conducting future cost-effectiveness analyses of DMTs for patients with MS.