The beta(2)-integrins are a subfamily of integrins expressed on leukocytes that play an essential role in leukocyte trafficking, activation, and many other functions. Studies in EAE, the animal model for multiple sclerosis, show differential requirements for beta(2)-integrins in this disease model, ranging from critical in the case of LFA-1 (CD11a/CD18) to unimportant in the case of CD11d/CD18. Importantly, expression of beta(2)-integrins on T cell subsets provides some clues as to the function(s) these adhesion molecules play in disease development. For example, transferred EAE studies have shown that Mac-1 (CD11b/CD18) expression on alphabeta T cells is critical for disease development, and the absence of LFA-1 on Tregs in recipient mice results in exacerbated disease. In this review, we summarize recent findings regarding the role of beta(2)-integrins in demyelinating disease and new information about the role of beta(2)-integrins with respect to alterations in Treg numbers and function. In addition, we discuss the potential for targeting beta(2)-integrins in human demyelinating disease in light of the recent animal model studies.