Acute kidney injury (AKI) is a widely held concern related to a substantial burden of morbidity, mortality and expenditure in the healthcare system. AKI is not a simple illness but a complex conglomeration of syndromes that often occurs as part of other syndromes in its wide clinical spectrum of the disease. Genetic factors have been suggested as potentially responsible for its susceptibility and severity. As there is no current cure nor an effective treatment other than generally accepted supportive measures and renal replacement therapy, updated knowledge of the genetic implications may serve as a strategic tactic to counteract its dire consequences. Further understanding of the genetics that predispose AKI may shed light on novel approaches for the prevention and treatment of this condition. This review attempts to address the role of key genes in the appearance and development of AKI, providing not only a comprehensive update of the intertwined process involved but also identifying specific markers that could serve as precise targets for further AKI therapies.