Multiple sclerosis is believed to be an autoimmune disease with an end-point of neuro-degeneration, but in which inflammation plays a predominant role. Therefore therapies which target inhibition of the excessive recruitment of leukocytes into the central nervous system (CNS) are actively sought after by medical research. Drug discovery relies heavily on animal models used for such research, called Experimental Autoimmune Encephalomyelitis (EAE). Several chemokines and their receptors have been shown to play a role in this recruitment into the CNS, and we have investigated several strategies which antagonize this system in EAE models. We will discuss these strategies and their successes and failures to prevent disease symptoms and the insights they have provided.