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Maintaining vascular barrier competence, preventing interstitial edema, and keeping microcirculation intact is crucial to achieve an optimal outcome in cardiopulmonary bypass surgery (CPB). Blood contact with roller pumps and foreign surfaces during CPB induces shear stress and a pressure drop across the pump boot that leads to transient systemic activation of the inflammatory and hemostatic systems. Moreover, patients after CPB often need volume resuscitation using the smallest possible amount of colloid solution because of fluid overload. For this purpose, human-derived albumin may be preferred over synthetic colloids because CPB priming with albumin preserves oncotic pressure, prevents platelet adhesion, and likely induces less consumption of coagulation factors. In patients with increased bleeding or renal failure, albumin is a safe alternative because of its minimal side effects. Large, randomized clinical trials comparing the benefit of albumin versus other fluids are warranted in the future to define albumin's distinct role in select high-risk surgical populations., (© The Author(s) 2014.)