The kidney undergoes continuous, slow cellular turnover for tissue maintenance and rapid cell replacement after injury. The cellular origin of newly differentiated tubular epithelium remains controversial. In some non-renal organs, adult stem cells are recognized as the cell of origin for tissue replacement, such as the hematopoietic system, intestine and skin. These findings have prompted intense investigation for evidence of renal stem cells because of the great need for new therapeutic approaches to treat acute kidney injury and chronic kidney disease. Early excitement at reports that bone marrow-derived cells transdifferentiate into renal epithelial cells has been tempered by findings that show such events to be rare or potentially explained by cell fusion. More recent studies have focused on the possibility that renal progenitors exist within the kidney. In this review we compare data supporting the existence of adult renal stem cells with the body of evidence indicating that the kidney regenerates by self-duplication of differentiated cells. The identification of adult renal epithelial progenitor cells will ultimately determine the future direction of renal regenerative medicine.