Significant advances have been made in understanding the pathophysiology of injury at the cellular level in ischemic acute renal failure. Alterations in the actin cytoskeleton are of central importance to the structural, physiological, and biochemical changes that occur in proximal tubule cells during acute ischemic injury. These cytoskeletal alterations occur rapidly and are dependent on the severity and duration of ischemic injury. Most importantly, alterations in the actin cytoskeleton are responsible for changes in the cell surface membrane that modify cell polarity, cell-cell interactions, and cell-matrix interactions. Ultimately, these cytoskeletal alterations play a major role in the decrement in glomerular filtration rate that is the hallmark of ischemic acute renal failure.