Epidemiologic studies applying the acute kidney injury (AKI) classification system have confirmed the increasing incidence of AKI in different settings and its association with adverse outcomes. AKI is now a recognized important risk factor for new-onset chronic kidney disease, determining acceleration in progression to end-stage renal disease, leading to poor quality of life, disability, and long-term costs. AKI has been associated with high mortalities; however, it is likely that a significant number of deaths associated with AKI could be avoided. This article reviews the key aspects of the 0by25 initiative and its application in critically ill patients.