Experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis, is characterised by microglial activation and lymphocytic infiltration. Lymphocytic activation through the antigen presentation process involves three main signals, the first provided by the engagement of major histocompatibility complex molecules (MHC) with the receptor of T-cells (TCR), the second by the binding of co-stimulatory molecules and the third by the secretion or expression of T-cell polarising molecules in specific populations of antigen presenting cells (APC). Microglial cells are considered to be the main APC population in the central nervous system (CNS). Specifically in EAE an increase in MHCs, costimulatory molecules and different T-cell polarizing factors have been reported in microglia. However, a growing number of evidences suggest that dendritic cells (DCs), the main APC in the peripheral immune system, may also participate in the regulation of T-cell responses within the CNS. In this review we summarize the principal knowledge regarding microglial/macrophage function in EAE and their role in T-cell modulation, as well as the participation of DCs in the immune response associated to this disease.