Development of the cardiovascular system through the last trimester of pregnancy and the subsequent neonatal period is profound. Morphological changes within the myocardium make the heart vulnerable to challenges such as fluid shifts and anesthetic drugs. The sensitivity of the myocardium to metabolic challenges and potential harm of drugs needed to maintain adequate blood pressure and cardiac output are highlighted. Traditional monitoring under anesthesia has focussed on maintaining oxygenation and heart rate in the neonate with less attention paid to blood pressure, cardiac output, and more importantly organ well-being. There is now a better understanding of the limitations of blood pressure homeostasis in the neonate and the potential consequences of marginal hypoperfusion. This article highlights some of these vulnerabilities particularly as they relate to anesthesia and surgery in the very young.