Acute kidney injury (AKI) is a significant cause of morbidity and mortality in hospitalized patients, especially those who are critically ill. The mortality rate in patients with severe AKI requiring renal replacement therapy (RRT) can exceed 50%[1]. Numerous factors contribute to the development of AKI, including reductions in renal blood flow, actions of nephrotoxic drugs, cellular injury/death of proximal tubule epithelial cells, pro-inflammatory responses of renal endothelial cells, influx and activation of inflammatory leukocytes that further reduces renal blood flow through vascular conges tion and promotes and extends injury to kidney parenchymal cells [2, 3]. The immune response in AKI involves cells of both the innate and adaptive immune systems. Although numerous studies have demonstrated the detrimental role of many different types of immune cells, recent reports have uncovered a protective and possibly therapeutic role of other immune cells in AKI. Studies in animal models of AKI have revealed that innate immune cells, such as neutrophils, macrophages, dendritic cells, natural killer (NK) cells and natural killer T (NKT) cells, and adaptive CD4+ T cells promote renal injury. Indeed, renal inflammation is a common feature of human AKI [4] and detailed analyses of biopsy samples from patients with AKI demonstrated the presence of mononuclear leukocytes (some CD3+ T cells) and neutrophils [5]. In contrast, CD4+FoxP3+ regulatory T cells (Tregs) can protect the kidney from ischemic and nephrotoxic injury in animal models. Understanding the immune mechanisms of renal injury and protection should yield new approaches to prevention and treatment of AKI.