Toll-like receptors (TLRs) are evolutionarily conserved trans-membrane receptors that detect microorganisms through the recognition of conserved molecular motifs. With each TLR able to recognize a discrete set of microbial ligands, TLRs represent an important mechanism by which the host detects a variety of microorganisms. Triggering of TLRs by pathogens is classically understood to result in an inflammatory immune response that supports the subsequent clearance of the offending microbe. However, animals are stably colonized by a consortium of symbiotic microbes (the microbiota) that possess many of the same structural motifs as pathogens, which raises the question of how the host is able to peacefully coexist with this community of organisms without suffering from chronic inflammatory disease. Paradoxical to its proinflammatory role during infection, recent studies have suggested that commensal bacterial recognition by TLRs is important for limiting inflammation within the intestine. While TLR expression on cells of the innate immune system (macrophages and dendritic cells) is largely thought to account for TLR function, cells of the adaptive immune system (T and B cells) and nonhematopoietic (epithelial) cells also express TLRs. Recent evidence has uncovered that the functional consequence of TLR engagement depends largely on the responding cell type and does not always result in inflammation. In this article authors will highlight how TLR engagement on epithelia, B and T cells promotes mutually beneficial interactions between hosts and their resident microbes.