One important pillar of cellular immune defense in mammals is the T-lymphoid compartment which produces cells that are able to specifically recognize foreign peptide antigens through a membrane-bound receptor. These T-cells can trigger a variety of defense mechanisms upon antigen stimulation ranging from the production of potent cytokines to the direct killing of virus-infected cells. The production of such highly specialized T-cells takes place in the thymus and requires a stringent process of differentiation and selection of precursor cells that are delivered from the bone marrow. In the thymus, several waves of proliferative expansion and selection ensure the production of a large repertoire of antigen-specific T-cells that each bear a unique T-cell receptor (TCR) which is able to recognize foreign antigens but can tolerate the own host-specific peptide structures. Education of precursors to mature T-cells in the thymus requires a dense network of regulatory processes acting at receptor-ligand interactions, signal transduction, genomic rearrangement of TCR gene loci, cell cycle progression, transcriptional control and programmed cell death.