The zebrafish has become a significant model system for studying renal organogenesis and disease, as well as for the quest for new therapeutics, because of the structural and functional simplicity of the embryonic kidney. Inroads to the nature and disease states of kidney-related ciliopathies and acute kidney injury (AKI) have been advanced by zebrafish studies. This model organism has been instrumental in the analysis of mutant gene function for human disease with respect to ciliopathies. Additionally, in the AKI field, recent work in the zebrafish has identified a bona fide adult zebrafish renal progenitor (stem) cell that is required for neo-nephrogenesis, both during the normal lifespan and in response to renal injury. Taken together, these studies solidify the zebrafish as a successful model system for studying the broad spectrum of ciliopathies and AKI that affect millions of humans worldwide, and point to a very promising future of zebrafish drug discovery. The emphasis of this review will be on the role of the zebrafish as a model for human kidney-related ciliopathies and AKI, and how our understanding of these complex pathologies is being furthered by this tiny teleost. Birth Defects Research (Part C) 93:141–156, 2011. © 2011 Wiley-Liss, Inc.