Fluid management is a complex yet fundamental aspect in the care of patients undergoing cardiac surgery, and different to that for patients in general intensive care and other surgical specialties. The underlying cardiac disease and impaired cardiovascular reserve of patients in this high-risk population means that significant hemodynamic alterations can impact adversely on their short- and long-term outcomes. Volume replacement during and after cardiac surgery is not influenced by filling pressures in isolation, but requires a critical balance with vasomotor tone, fluid responsiveness and cardiac contractility. The timing, type, volume and monitoring of fluid administration are important considerations. So far, the evidence does not favor a specific choice of fluid therapy and none of the available fluid therapies has been assessed for comparative endothelial homeostatic potential. This leaves a significant knowledge gap and an incentive for researchers, clinicians and industry to design and test safer and more efficacious choices for clinical use.