Cardiac surgery utilizing cardiopulmonary bypass has come a long way since its introduction nearly 60 years ago. In the early days, end-organ damage was linked to contact of the blood with the extracorporeal circuit. One potential cardiac surgery complication known to result in significant morbidity and mortality is acute kidney injury (AKI). Causes of AKI are multifaceted, but most of them are associated with techniques that perfusionists employ during extracorporeal circuit management. These can cause patients to either go on dialysis or renal replacement therapy. Patients with AKI have longer lengths of stay and consume significant resources beyond those with normal kidney function. Few current evidence-based markers determine if the kidneys are adequately protected during surgery. Most relevant literature does not address perfusion-specific techniques that reduce the incidence of AKI. This paper reviews the pathophysiology of the kidney and focuses on perfusion techniques that may reduce the incidence of AKI.