Physiologic-based management of hemodynamic instability is proven to guide the logical selection of cardiovascular support and shorten the time to clinical recovery compared to an empiric approach that ignores the heterogeneity of the hemodynamic instability related mechanisms. In this report, we classified neonatal hemodynamic instability, circulatory shock, and degree of compensation into five physiologic categories, based on different phenotypes of blood pressure (BP), other clinical parameters, echocardiography markers, and oxygen indices. This approach is focused on hemodynamic instability in infants with normal cardiac anatomy.Conclusion: The management of hemodynamic instability is challenging due to the complexity of the pathophysiology; integrating different monitoring techniques is essential to understand the underlying pathophysiologic mechanisms and formulate a physiologic-based medical recommendation and approach. What is Known: • Physiologic-based assessment of hemodynamics leads to targeted and pathophysiologic-based medical recommendations. What is New: • Hemodynamic instability in neonates can be categorized according to the underlying mechanism into five main categories, based on blood pressure phenotypes, systemic vascular resistance, and myocardial performance. • The new classification helps with the targeted management and logical selection of cardiovascular support.