A miniaturized cardiopulmonary bypass circuit enables the safe performance, in selected pediatric patients, of bloodless open heart surgery. As the latest survival rates in neonatal and infant cardiac surgery have become satisfactory, investigators have concentrated upon the improvement of existing procedures. Institutional guidelines and multidisciplinary efforts undertaken in the pre- and postoperative periods are of great importance, concerning bloodless CPB and should be seriously pursued by all involved caregivers. This review reflects upon the selective, most relevant requirements for success of asanguinous neonatal and infant CPB: acceptable level of hemodilution during the CPB, patient preoperative hematocrit value and volume of CPB circuit. We present an assessment of practical measures that were also adapted in our institution to achieve an asanguinous CPB for neonatal and infant patients.