Acute kidney injury (AKI) occurs in as many as 40% of patients after cardiac surgery and requires dialysis in 1% of cases. Acute kidney injury is associated with an increased risk of mortality and morbidity, predisposes patients to a longer hospitalization, requires additional treatments, and increases the hospital costs. Acute kidney injury is characterized by a progressive worsening course, being the consequence of an interplay of different pathophysiologic mechanisms, with patient-related factors and cardiopulmonary bypass as major causes. Recently, several novel biomarkers have emerged, showing reasonable sensitivity and specificity for AKI prediction and protection. The development and implementation of potentially protective therapies for AKI remains essential, especially for the relevant impact of AKI on early and late survival.