The early recognition and management of sepsis remain the greatest challenges in the field of critical care medicine. Endothelial injury is one of the hallmarks of sepsis, leading to capillary leak, microcirculatory dysfunction, organ failure, and eventual death in many critically ill patients. The angiogenic growth factors, angiopoietin (angpt)-1 and angpt-2, act upon the Tie-2 receptor in opposing roles. Angpt-2 has been found in abundance in septic patients when compared with healthy controls. In the study by Kümpers and colleagues in the previous issue of Critical Care, angpt-2 levels correlated with markers of tissue hypoxia, disease severity, and mortality in septic adults. However, the temporal kinetics of the angiopoietins were not assessed. It remains to be seen whether angpt-2 levels will function solely as an early marker of sepsis or whether the manipulation of the angpt/Tie-2 system will become a rational therapeutic target for the management of sepsis.