Summary Multiple sclerosis (MS) is a neurological disorder that strikes the central nervous system. Due to the complexity of this disease, healthcare sectors are increasingly in need of shared clinical decision-making tools to provide practitioners with insightful knowledge and information about MS. These tools ought to be comprehensible by both technical and non-technical healthcare audiences. To aid this cause, this literature review analyzes the state-of-the-art decision support systems (DSSs) in MS research with a special focus on model-driven decision-making processes. The review clusters common methodologies used to support the decision-making process in classifying, diagnosing, predicting, and treating MS. This work observes that the majority of the investigated DSSs rely on knowledge-based and machine learning (ML) approaches, so the utilization of ontology and ML in the MS domain is observed to extend the scope of this review. Finally, this review summarizes the state-of-the-art DSSs, discusses the methods that have commonalities, and addresses the future work of applying DSS technologies in the MS field.