Multiple sclerosis (MS) is considered an immune-mediated disorder in which immune cells cross the blood-brain barrier to enter the central nervous system (CNS) wherein they augment the neuropathology of the disease. This chapter discusses the role of various immune cell types that contribute to the development and progression of MS. Specifically, the role of T cells, antigen-presenting cells, and components of the innate immune system such as macrophages, B cells, and the complement system are discussed. The involvement of CNS-specific cells such as microglia, astrocytes, and neurons in MS are discussed and the immunosuppressive role of regulatory T cells is considered. We introduce the involvement of chemokines and matrix metalloproteinases which helps recruit immune cells into the CNS in MS. Although the causes of MS are unknown, various factors such as genetic influences, environmental effects, and involvement of infectious agents as potential contributors to MS immune dysfunctions are also considered. With this background, we discuss the mechanisms of the immunomodulators that are used to treat MS.