Molecular mechanisms of inflammatory leukocyte accumulation in the central nervous system (CNS) have been addressed during the past fifteen years, using small-animal model systems. Identification of the molecules responsible for leukocyte-endothelial adherence, and the elucidation of the roles of chemokines, has promoted further understanding. These insights have become clinically relevant, as attested by ongoing and contemplated multiple sclerosis (MS) treatment trials.