Regulatory T-cells (Treg) represent a subset of CD4+ T-cells characterized by high suppressive capacity, which can be generated in the thymus or induced in the periphery. The deleterious phenotype of the Scurfy mouse, which develops an X-linked lymphoproliferative disease resulting from defective T-cell tolerance, clearly demonstrates the importance of Treg cells for the maintenance of immune homeostasis. Although significant progress has been achieved, much information regarding the development, characteristics and function of Treg cells remain lacking. This chapter highlights the most recent discoveries in the field of Treg biology, focusing on the development and role of this cell subset in the maintenance of immune balance.