Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) manifested with varying clinical course, pathology, and inflammatory patterns. There are multiple animal models that reflect different aspects of this heterogeneity. Collectively, these models reveal a balance between pathogenic and regulatory CD4⁺ T cells, CD8⁺ T cells, and B cells that influences the incidence, timing, and severity of CNS autoimmunity. In this review we discuss experimental autoimmune encephalomyelitis (EAE) models that have been used to study the pathogenic and regulatory roles of these immune cells; models that recapitulate different aspects of the disease seen in patients with MS, and questions remaining for future studies.