Determining how the pulmonary vascular system is formed, maintained, or disrupted during development and disease represents a major challenge in contemporary lung biology. Whereas it is appreciated that cellular proliferation, differentiation, migration, and apoptosis need to be carefully controlled in order to attain pulmonary vascular homeostasis, knowledge of the underlying cellular and molecular mechanisms involved remains surprisingly limited. Because homeobox genes represent master regulators of organogenesis and tissue patterning, it is likely that these transcription factors play a critical role in the formation of blood vessels within the lung, as well as in pathologic states in which the highly ordered structure of the pulmonary vascular tree is compromised. The aim of this review is to discuss some of the known functions of homeobox genes in the vasculature, and to extrapolate these findings to their potential roles in developing and diseased pulmonary vessels.