Acute Kidney Injury (AKI) is a common complication after cardiac surgery affecting up to 40% leading to increased morbidity and mortality. To date, there is no specific treatment for AKI, thus, clinical research efforts are focused on preventive measures. The only pharmacological preventive intervention that has demonstrated a beneficial effect on AKI in a high-quality, double-blind, randomized controlled trial is a short perioperative infusion of a balanced mixture of amino acid solution. Amino acid infusion reduced the incidence of AKI by recruiting renal functional reserve and, therefore, increasing the glomerular filtration rate. The beneficial effect of amino acids was further confirmed for severe AKI and applied to patients with chronic kidney disease. Among non-pharmacological interventions, international guidelines on AKI suggest the implementation of a bundle of good clinical practice measures to reduce the incidence of perioperative AKI or to improve renal function whenever AKI occurs. The Kidney Disease Improving Global Outcomes (KDIGO) bundle includes the discontinuation of nephrotoxic agents, volume status and perfusion pressure assessment, renal functional hemodynamic monitoring, serum creatine, and urine output monitoring, and the avoidance of hyperglycemia and radiocontrast procedures. However, pooled data from a meta-analysis did not find a significant reduction in AKI. The aim of this review is to delineate the most appropriate evidence-based approach to prevent AKI in cardiac surgery patients.