Abstract Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are antagonistic ligands that bind to the extracellular domain of the Tie-2 receptor, which is almost exclusively expressed by endothelial cells. Angiopoietins can directly stimulate both endothelial cells and neutrophils for an overall proinflammatory and proangiogenic response. An increasing number of experimental and clinical studies gave evidence that in the course of sepsis the serum levels of Ang-1 and Ang-2 as well as their ratio significantly differ from those in healthy subjects, in non-septic hospitalized patients, and in patients with non-infectious systemic inflammatory response syndrome (SIRS) or critical illness. Further evidences have demonstrated that the magnitude of Ang-2 dysregulation correlates with the severity of sepsis and the mortality rate. Since the onset of neonatal sepsis is often subtle and the diagnosis occurs later, Ang-1 and Ang-2 appear to be very promising biomarkers for improving the diagnosis and the management of septic newborns.