This chapter discusses the cardiac system development in detail. It describes the incidence and risk factors for the development of congenital heart disease (CHD), and the clinical presentation of an infant with CHD. The chapter also discusses cyanotic heart defects, acyanotic defects, and rhythm disturbances in neonates. CHD is one of the more common birth defects, occurring in six to 13 per 1,000 births as the result of genetic or environmental factors. Of these infants, 25% have critical CHD requiring intervention. A delay in diagnosis of critical CHD compromises neonatal outcome. CHD is the most common genetic anomaly and the leading noninfectious cause of death during the first year of life. Cardiac development is a complex multifactorial process involving a convergence of risk factors resulting in CHD. Congenital disorders of the cardiac system, if left untreated, will compromise neonatal well-being and survival.