This review focuses on the effects of the agents currently approved (or in late clinical trials) as therapies for multiple sclerosis (MS) on the glial cell populations of the central nervous system (CNS). These are comprised of astrocytes, microglia, and oligodendrocytes (OLs), and their progenitors (OPCs). Although the efficacy of these agents is to date established only for the relapsing component of the disease and linked to effects on the systemic immune system, each has been examined with regard to effects on the CNS compartment. The impact of therapies on glia would include modulating these cells immune reactivity, which is considered to underlie the tissue injury process in MS and to any subsequent repair process. As reviewed, these agents can exert their effects either indirectly by modulating the constituents of the systemic immune system or directly depending on their capacity to traverse the blood brain barrier (BBB). Most available data has been derived from administration of these agents in animal models or application to glial cells in vitro. The challenge remains of translating these observations into effective means to impact on the progressive course of disease and reverse existent disabilities.