The rebirth of interest in suppressor T cells has spawned a vast amount of data that shed light on their biology and role in immune system homeostasis. Since the early studies on the naturally occurring CD4+/CD25+ T regulatory cells, much attention has been focused on ways to induce suppressor T cells in vivo. This review discusses the salient features of the induction of antigen-specific suppressor T cells in a T cell receptor (TCR) transgenic mouse model of experimental allergic encephalomyelitis (EAE) in response to epicutaneous immunization with cognate peptide. We discuss the skin environment as a privileged anatomical site for therapeutic intervention against pro-inflammatory auto-immune disorders using non-invasive approaches for antigen delivery.