A plethora of genes involved in murine B and T cell development have been identified, and developmental pathways within the primary lymphoid tissues have been well delineated. The generation of a functional, but non‐self reacting lymphocyte repertoire results from the completion of several checkpoints during lymphocyte development and competition for survival factors in the periphery. Improved knowledge of these developmental checkpoints and homeostatic mechanisms is critical for understanding human immunodeficiency, leukaemia/lymphoma and autoimmunity, which are conditions where checkpoints and homeostasis are likely to be deregulated.