Autoimmune diseases have been increasing in incidence in recent decades, especially in industrialized countries. As of today these represent a major public health problem that has called for complex therapeutic approaches. These include the development of biotechnology-derived products such as humanized monoclonal antibodies or fusion proteins that target membrane receptors of immune cells or cytokines involved in the pathogenesis of autoimmune diseases. Major disease-modifying drugs have emerged that have revolutionized the management of rheumatoid arthritis, multiple sclerosis and others. Presented here are the premises that led to the development of these agents, and the conditions of their current use in autoimmune disease. Despite the major advances, most of these therapies clearly do not provide a real cure of autoimmune diseases as their effect is not specific for the autoantigen-induced responses and, importantly, their time span of activity is limited, and self-tolerance is not restored. In other words, our newly-enriched drug armamentarium of immunomodulatory and anti-inflammatory molecules still does not provide for a radical and durable solution to autoimmunity. However gratifying exceptions to this do exist, in particular monoclonal antibodies specific for the CD3 complex, the transducing element of the T cell antigen receptor, with experimental data having been successfully translated to the clinic for therapy of recent-onset autoimmune diabetes mellitus, with an ensuing and sustained remission (up to 4 years) after just a single short course of treatment. Other such successes can be anticipated.