Acute kidney injury (AKI) is a common complication of severe sepsis. Severe sepsis is the most common cause of AKI in ICU. The widely accepted and practiced initial cornerstone of treatment for septic AKI is fluid resuscitation. The biological rationale for fluid resuscitation in septic AKI is based on the assumption that septic AKI is an ischemic form of AKI and that increasing renal perfusion and oxygen delivery by means of fluid resuscitation will protect the kidney. Whether this is true, however, remains uncertain. In this paper, we discuss salient pathophysiological aspects of AKI, review the evidence available on the need for fluid resuscitation, the amount and the type of fluid that might be best suited to AKI and discuss all major aspects of fluid resuscitation for septic AKI in humans and experimental animals.