TLRs belong to a family of pattern recognition receptors (PRRs) that recognize highly conserved microbial antigens termed pathogen associated molecular patterns (PAMPs). So far, ten TLRs have been identified in human genome. Each TLR senses a different set of microbial stimuli, and recruits various of adaptors and activates a series of distinct signaling cascades, and drives specific responses against the pathogens. TLRs bridged innate and adaptive immunity. The discoveries of Toll-like receptors guided the field of innate immunity to its present era of accelerated advancement. In this review, we will focus on the recent progresses of TLRs-mediated signaling. A better understanding of the immunological and molecular mechanisms mediated by TLRs will obviously facilitate the exploiting molecular targets of immunotherapy to control TLR-mediated diseases.