Immune tolerance ensures that the immune system responds to foreign molecules and not to self-molecules. When tolerance breaks down, severe, self-destructive diseases such as rheumatoid arthritis, lupus, and multiple sclerosis may develop. Understanding the mechanisms involved in establishing and maintaining immune tolerance is essential for effectively treating these autoimmune diseases. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology reviews how self- tolerant T- and B-cell populations are produced. The contributors discuss the elimination of autoreactive lymphocytes during their development in the thymus and bone marrow, the suppression of autoreactive cells by regulatory T cells in the periphery, and intrinsic mechanisms that produce clonal anergy. The roles of dendritic cells in antigen presentation and mechanisms that prevent autoreactivity in natural killer cells are also covered. Including discussions of autoimmune diseases, their genetic bases, and therapeutic strategies, this volume is a valuable reference for all immunologists and clinicians wishing to understand or develop treatments for autoimmune diseases.