Pentalogy of Cantrell is a constellation of five congenital defects that pose a unique challenge for surgeons. Defects of the heart, pericardium, diaphragm, sternum, and anterior abdominal wall are pathognomonic. Although the incidence is low, it is critical to identify it in a timely fashion in order to adequately address all aspects. Early diagnosis, supportive care, and strategic surgical planning with a multidisciplinary team are all key components in managing patients with Pentalogy of Cantrell. In this text we sought to explore the evolution of both the understanding and treatment for this complex entity and provide current recommendations to today's pediatric caregivers.