The mammalian Toll-like receptor (TLR) family, consisting of 13 members, plays an important role in innate recognition of specific patterns of microbial products. TLR-dependent recognition subsequently causes an activation of antigen-specific adaptive immunity. TLR-mediated signaling pathways consist of two pathways that induce gene expression: the myeloid differentiation primary response gene 88 (MyD88)-dependent pathway and Toll/interleukin-1 receptor-domain containing adaptor protein-inducing interferon--dependent pathway. Synthetic TLR agonists, as well as TLR antagonists, affect and manipulate the host defense systems, and some of these immunomodulating agents may help to overcome intrinsic disturbances of the TLR system to offer new treatment options in urinary tract infection (UTI). Future studies are necessary to clarify additional associations between TLRs and severity of UTI, which may help in developing new treatment options.