Over the past 20 years, the Pediatric Cardiovascular Department at Penn State Health Children’s Hospital and College of Medicine has been researching ways to improve the safety and efficacy of pediatric cardiopulmonary bypass (CPB) for neonates and children requiring congenital heart surgery. One of the long-standing projects within our research group has been the assessment of pulsatile flow during CPB. The purpose of this essay is to summarize our findings of pulsatile flow during CPB and to describe how this may facilitate improved clinical outcomes for neonates and children undergoing congenital heart surgery.