This volume focuses on challenging field in biomedicine that is the genetic control of central immune tolerance. It covers the thymus development, their cellular components and their respective function, the peculiar gene expression profiling (transcriptome) found in the medullary thymic epithelial cells (mTECs) that are implicated in the self-representation in the thymus, the Autoimmune regulator (Aire) gene, the mutations in this gene and manifestation of autoimmune diseases, and the role of cell-cell interactions within the thymus with implications in the negative selection (elimination) of nascent autoreactive T cells in preventing aggressive autoimmunity. The thymus gland is a lymphoid organ implicated in the maturation, differentiation and selection of T cells. This organ is gained more and more attention in different biomedical research labs worldwide due to its function that is associated with the control of immune homeostasis in the body, establishing the central immune tolerance and preventing the onset of autoimmune diseases.