Abnormalities in the pulmonary vasculature are associated with many forms of lung injury. This chapter reviews current understanding of normal pulmonary vascular development and function, and the potential mechan- isms that result in clinical manifestations of lung injury. The growth of the pulmonary vascular bed, and the mechanisms that regulate vascular tone are also discussed (additional details on lung growth and development are in Chapter 2). Relevant examples of pulmonary vascular diseases are presented, concentrating primarily on fetal and neonatal disorders. Pulmon- ary hypertension secondary to congenital heart disease is associated with vascular remodeling. Abnormal structural development of the pulmonary vasculature has also been implicated in persistent pulmonary hypertension of the newborn (PPHN), a condition that accounts for 1% of all admissions to newborn intensive care units. Irregular vascular reactivity and morphology have also been well characterized in adult patients with primary and secondary pulmonary hypertensive disorders. Vascular dysfunc- tion is thought to play a significant role in the pathophysiology of both acute lung injury (ALI) and chronic lung injury in children and adults. Relevant animal models of lung injury and vascular dysfunction, and the insights they provide in identifying underlying mechanisms are discussed in this chapter. Potential therapeutic strategies resulting from this knowl- edge are also described, with further details about vascular-based therapies for clinical lung injury given in Chapter 17.