Acute kidney injury (AKI) is a major medical problem in critical illness, and has a separate independent effect on the risk of death. Septic shock and cardiac surgery utilizing cardiopulmonary bypass are the two most common factors contributing to AKI. Clinical predictors and biochemical markers identified for the development of AKI can only explain a part of this individual risk. Another tool to predict the risk of AKI and to improve individualized patient care focuses on the identification of genetic risk factors which might be involved in the development of AKI. However, to date our knowledge on the importance of such genetic polymorphisms in influencing the susceptibility to and severity of AKI remains limited. There is evidence that several genetic polymorphisms accounting for sepsis- or cardiopulmonary bypass-associated AKI involve genes which participate in the control of inflammatory or vasomotor processes. In this article, we will review current knowledge concerning the role of genetic polymorphism in the pathogenesis of sepsis- and cardiopulmonary bypass-associated AKI and discuss possible areas for future developments and research in this field.