Publisher Summary Multiple sclerosis (MS) is an autoimmune disorder in which the central nervous system (CNS) is targeted by the dysregulated activity of the immune system, resulting in focal lesions and progressive neurological dysfunction. MS is heterogeneous in its clinical symptoms, rate of progression, and response to therapy, probably reflecting the existence of several pathogenic mechanisms that make different contributions to the disease. MS is a T-cell-mediated autoimmune disease thought to result from a combination of genetic and environmental factors. This chapter analyzes the contribution of genomics, transcriptomics, immunomics, and proteomics in delineating these factors. The utility is in monitoring disease progression and response to therapy, identifying new targets for therapeutic intervention, and detecting individuals at risk of developing the disease later on in life. The first observation suggesting a genetic contribution to MS susceptibility was the identification of familial aggregation. First, second, and third degree relatives of MS patients have an increased risk of developing the disease. There are two approaches that are used for the identification of genes linked to MS pathogenesis and progression—linkage and association mapping. The autoimmune nature of MS suggests that the study of the immune response should be useful for the early diagnosis, prognosis, and monitoring of MS patients.