Neonatal Respiratory Distress Syndrome (RDS), caused by surfactant deficiency, is a primary cause of neonatal morbidity and mortality in premature infants in the United States. The pathophysiology of RDS, however, involves more than surfactant deficiency and decreased pulmonary compliance. There is an intricate interaction of pulmonary and cardiovascular contributors to the pathophysiology. The consequences of the treatment of RDS and its associated morbidities may increase the risk for additional morbidities. The purpose of this review is to describe the cardiovascular responses to RDS and its treatment in preterm infants. Topics include the significance of the cardiovascular system in the natural history and treatment of RDS, from antenatal care through the evolution of chronic lung disease. The discussion reviews what is known, what needs to be known, and how neonatologists may increase their awareness of these underappreciated consequences in the future.