Toll like receptors (TLRs) have been extensively studied since their discovery in 1997, and an increasingly detailed picture is emerging about their role in health and disease. TLRs, the first identified family of pattern recognition receptors, can recognize invaders 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 are thought to play a significant role in immune activation to pathogens, as well as the development and course of various kidney pathologies. This review summarizes the present data about the important role TLRs play in kidney diseases focusing on the specific role of PAMPs versus DAMPs and of local versus systemic TLR activation.