The pathophysiology of acute renal failure in sepsis is complex and includes intrarenal vasoconstriction, infiltration of inflammatory cells in the renal parenchyma, intraglomerular thrombosis, and obstruction of tubuli with necrotic cells and debris. Attempts to interfere pharmacologically with these dysfunctional pathways, including inhibition of inflammatory mediators, improvement of renal hemodynamics by amplifying vasodilator mechanisms and blocking vasoconstrictor mechanisms, and administration of growth factors to accelerate renal recovery, have yielded disappointing results in clinical trials. Interruption of leukocyte recruitment is a potential promising approach in the treatment of septic acute renal failure, but no data in humans are presently available. Activated protein C and steroid replacement therapy have been shown to reduce mortality in patients with sepsis and are now accepted adjunctive treatment options for sepsis in general.