The parathyroid and thymus glands have diverse physiological roles but a common embryonic origin. This chapter reviews initial patterning and the early development of these organs and molecular mechanisms controlling these processes. It explains potential mechanisms for the evolution of these organs, which may have involved the same molecular pathways and describes possible models for the differentiation of embryonic and fetal parathyroid and thymic epithelial progenitor or stem cells. These organs play a variety of essential physiological roles, from the regulation of calcium homeostasis to the generation of T-cells required for adaptive immunity. Significant progress has been made in identifying the transcription factors required for thymus-parathyroid organogenesis. Little is known about intercellular signaling pathways acting at the site of thymus-parathyroid induction and regulating early organogenesis.