Endothelial cells (ECs) develop organ-specific gene expression and function in response to signals from the surrounding tissue. In turn, ECs can affect organ development and morphogenesis and promote or hinder disease response. In the lung, ECs play an essential role in gas exchange with the external environment, requiring both a close physical connection and a strong axis of communication with alveolar epithelial cells. A complete picture of the composition of the pulmonary endothelium is therefore critical for a full understanding of development, maintenance, and repair of the gas exchange interface. Defining the factors that control lung-specific EC specification, establish EC heterogeneity within the lung, and promote the differing contributions of EC subtypes to development, health, and disease will facilitate the development of much-needed regenerative therapies. This includes targeting therapeutics directly to ECs, developing pluripotent or primary cell-derived ECs to replace damaged or diseased vasculature, and vascularizing engineered tissues for transplant.