Sepsis-induced acute kidney injury (AKI) is the most common form of AKI observed in critically ill patients. AKI mortality in septic critically ill patients remains high despite our increasing ability to support vital organ systems. This high mortality is partly due to our poor understanding of the pathophysiological mechanisms of sepsis-induced AKI. Recent experimental studies have suggested that the pathogenesis of sepsis-induced AKI is much more complex than isolated hypoperfusion due to decreased cardiac output and hypotension. In nonresuscitated septic patients with a low cardiac output, a decrease in renal blood flow (RBF) could contribute to the development of AKI. In resuscitated septic patients with a hyperdynamic circulatory state, RBF is unchanged or increased. However, in resuscitated septic patients, sepsis-induced AKI can occur in the setting of renal hyperemia in the absence of renal hypoperfusion or renal ischemia. Alterations in the microcirculation in the renal cortex or renal medulla can occur despite normal or increased global RBF. Increased renal vascular resistance (RVR) may represent a key hemodynamic factor that is involved in sepsis-associated AKI. Sepsis-induced renal microvascular alterations (vasoconstriction, capillary leak syndrome with tissue edema, leukocytes and platelet adhesion with endothelial dysfunction and/or microthrombosis) and/or an increase in intra-abdominal pressure could contribute to an increase in RVR. Further studies are needed to explore the time course of renal microvascular alterations during sepsis as well as the initiation and development of AKI. Doppler ultrasonography combined with the calculation of the resistive indices may indicate the extent of the vascular resistance changes and may help predict persistent AKI and determine the optimal systemic hemodynamics required for renal perfusion.