Acute kidney injury (AKI) is a serious yet potentially reversible complication of sepsis. Several molecular mechanisms involved in the development of septic AKI have been identified. These mechanisms may be important targets in the development of future therapies. This review highlights the role of the innate immune response to sepsis and its downstream effects on kidney structure and function with special reference to the adaptive cellular response and glomerular hemodynamic changes. In addition, current evidence surrounding the management of patients with septic AKI is summarized. Finally, potential novel therapies for septic AKI are presented.