Autoimmune diseases are many, have an overall prevalence of about 3% of the world population, affecting more women than men, and their incidence is influenced by genetics and the environment. It is currently thought that the immune response of a genetically predisposed individual to an environmental pathogen, under the influence of inadequate or non-functional immunoregulatory mechanisms, can lead to the development of an autoimmune disease. Advances in the treatment of autoimmune diseases follow a better understanding of the abnormalities in the cellular activity pathways and the resulting, often permanent, imbalance of the pro- and anti-inflammatory cytokine expression profiles. Over the past few years, there has been a dramatic change in the therapeutic regimens employed in autoimmune diseases, with soluble receptors, monoclonal antibodies and molecular mimetics enhancing or gradually replacing conventional immunosuppressive therapies. New biologicals have been developed, targeting defined pathways of the adaptive immune response. One approach towards the therapeutic management of autoimmune diseases involves the design and use of peptide analogs of disease-associated epitopes to be used as immunomodulatory drugs. Peptides can target cell-functions directly, by interfering with the formation of the tri-molecular complex MHC-Peptide-TCR, and/or they can target soluble mediators such as cytokines or their receptors, eventually replacing monoclonal antibody therapies. This review offers an update on the treatment modalities of certain prototypic autoimmune diseases, based on the current knowledge of disease pathogenesis, with emphasis on cell activation and cytokine expression profiles.