Glatiramer acetate (GA) (Copolymer-1, Copaxone, Teva, Israel, YEAK) is a polypeptide-based therapy approved for the treatment of relapsing-remitting multiple sclerosis. Most investigations have attributed the immunomodulatory effect of GAs to its capability to alter T-cell differentiation. Specifically, GA treatment is believed to promote development of Th2-polarized GA-reactive CD4(+) T-cells, which may dampen neighboring inflammation within the central nervous system. Recent reports indicate that the deficiency in CD4(+)CD25(+)FoxP3(+) regulatory T-cells in multiple sclerosis is restored by GA treatment. GA also exerts immunomodulatory activity on antigen presenting cells, which participate in innate immune responses. These new findings represent a plausible explanation for GA-mediated T-cell immune modulation and may provide useful insight for the development of new and more effective treatment options for multiple sclerosis.