Acute kidney injury (AKI) has a high hospital incidence and is associated to significant morbidity and mortality. Sepsis, major surgery and low cardiac output are the main cause of AKI worldwide. In the majority of these situations, volume expansion is part of both prevention and therapeutic management, restoring peripheral perfusion and attenuating drug nephrotoxicity. Early and aggressive volume resuscitation in septic patients halts tissue ischemia and is associated with higher survival. However, a liberal fluid infusion strategy after six hours can cause fluid overload. Fluid overload has been associated with morbidity and mortality increase in critically ill patients. Herein, we present a review of the main studies that assessed the effects of net fluid balance/fluid overload on the morbidity and mortality of critically ill patients. We suggest that positive water balance may be used as a potential early biomarker of AKI in these patients.