Vitamin D deficiency is common in critically ill patients and associated with increased mortality, as well as an increased risk of acute kidney injury. The occurrence of acute kidney injury by itself substantially increases critical care mortality. In addition to regulating calcium and phosphorus homeostasis and bone metabolism, vitamin D has pleotropic effects on the immune response. Potential mechanisms of how a deficiency in vitamin D could predispose individuals to increased risk of acute renal failure include dysregulation of the immune system, predisposing patients to sepsis, endothelial dysfunction and prevention of healing of renal ischemia-reperfusion injury. Toll-like receptors, NF-κB and the renin-angiotensin-aldosterone system are mediators of vitamin D effects.