There is substantial evidence to demonstrate the benefits of goal-directed hemodynamic optimization using fluid loading or inotropic support or both to improve outcome during major surgery. However, until now, only limited pathophysiological data have been available to explain this benefit. The maintenance of adequate tissue perfusion and global oxygen delivery is an essential goal for therapy. In an interesting study, Jhanji and colleagues provided additional data that emphasize the roles of optimization of intravascular fluid status and low doses of inotropes to improve microvascular blood flow and tissue oxygenation. This commentary aims to highlight some issues raised by this important study and provides additional elements to further position these results.