Since the discovery of the Toll-like receptors and their crucial role as modulators of innate immunity, there has been increasing appreciation of their role in human health and disease. Toll-like receptor signaling is critical in defending against invading microorganisms, but sustained receptor activation is also implicated in the pathogenesis of inflammatory diseases. Here we review the role of Toll-like receptors and their endogenous ligands in various renal diseases, particularly their activation in the inflammatory response of ischemic kidney injury, organ transplantation, and immune-mediated glomerulonephritis.