“The subtle blood is urged forward by a long course through the lungs … and is poured from the pulmonary artery into the pulmonary vein, where the blood is mixed with inspired air.” So wrote Michael Servitus (1511–1553), a Spanish physician and theologian who was burnt at the stake for his beliefs. Although the contemporary pulmonary vascular biologist is unlikely to face such a fate, the field of lung vascular developmental biology is nevertheless fraught with historic and technical obstacles that have impaired evolution of a unified theory of lung vascular development. On the other hand, tremendous advances have been made in comprehending morphogenesis of the lung at the level of the epithelium. When coupled with the knowledge that a dynamic and reciprocal relationship exists between the developing lung epithelium and their endothelial cell (EC) neighbors, the time appears ripe to re-evaluate the mechanisms controlling genesis of the pulmonary circulation. What is more, the recognition that a cache of postnatal lung diseases that perturb or destroy respiratory function may arise, in part, as a result of pulmonary vascular defects underscores the need to re-examine the “lesser circulation” (known as such because the flow path is short and lower pressure is required for it to operate efficiently), not only within its unique historical context, but also in the setting of modern biology. In fact, recent discoveries in fields as diverse as developmental biology, in silico modeling, and stem cell and gene therapy suggest that this time already has arrived.