Toll-like receptors (TLRs) are the first identified and best studied family of pattern recognition receptors. Expressed in immunocytes, TLRs initiate innate immune responses and concurrently shape the subsequent adaptive immune response. They are sensors of both pathogens, through the exogenous pathogen-associated molecular patterns (PAMPs), and tissue injury, through the endogenous danger-associated molecular patterns (DAMPs). In addition to immunocytes, TLRs are widely distributed in various cell types, including renal cells where they contribute significantly to various pathologies. In particular, many experimental and emerging clinical data indicate that TLRs are involved in the pathogenesis of urinary tract infections, sepsis-induced renal failure, kidney ischemia/reperfusion injury, idiopathic or systemic autoimmunity-induced glomerulonephritis and ultimately is renal fibrosis, which leads to end-stage renal disease. This review summarizes the present data about the important role TLRs play in the above kidney diseases focusing on the specific role of PAMPs versus DAMPs and of local versus systemic TLR activation.