Cytokines play an important role in the pathogenesis of inflammatory diseases including multiple sclerosis (MS). Experimental models have played a critical role in unraveling the roles of individual cytokines in this disease; however, these studies occasionally yield conflicting results, highlighting the complex role cytokines play in the disease process. Efforts to modulate cytokine function in MS have shown that effective treatments alter cytokine expression in the central nervous system (CNS) and in activated mononuclear cells, indicating that they are important therapeutic targets. In this review, we will summarize the current knowledge on the role of cytokine pathways in MS and what we learned from investigation of its animal model: experimental autoimmune encephalomyelitis (EAE).