Immunotherapeutic approaches to autoimmune disease have a common goal of inducing antigen-specific, long-lasting tolerance to autoantigens, without otherwise compromising the immune response. Here we review some of the most interesting experimental advances in this area. We discuss the use of T cell targeting drugs that have been reported to induce long lasting tolerance to ocular antigens. Strategies involving the targeting of idiotypic and clonotypic determinants associated with ocular autoimmunity, such as idiotypic network manipulation and T cell vaccination, are reviewed. The use of cytokines to promote perturbation of the Th1/Th2 balance with its possible implications for treatment of uveitis, is analysed. Finally, we review tolerogenic strategies based on acquisition of tolerance following presentation of antigen through alternative routes, such as injection of antigen into the anterior chamber, intravenous infusion of antigen, and oral administration of retinal antigens. Special emphasis is placed on the last strategy, since there are ongoing clinical trials using oral tolerance as an immunotherapeutic approach to treat autoimmune diseases, among them uveitis.