The innate immune system constitutes an efficient defense against invading microbial pathogens. Toll-like receptors (TLRs) eventually alert vertebrates about the presence of pathogens and elicit the immune responses. To date, 17 different TLRs have been identified in more than a dozen different fish species. Numerous studies revealed that specific piscine TLRs share functional properties with their mammalian counterparts. Nevertheless, remarkable distinct features of teleostean Toll-like receptor cascades have been discovered. A soluble TLR5 factor in rainbow trout for example might amplify danger signaling of membrane-bound TLR5 in a positive feed loop. Piscine TLR3 detects viral and additionally bacterial molecular patterns in contrast to mammalian TLR3. Regarding TLR4, the functional spectrum of this teleostean receptor is also different from its mammalian orthologue. While signaling quite similar as the mammalian counterpart in some fish species, it may down-regulate TLR activation in others or was even lost during evolution. The orthologues of human TLR6 and TLR10 are also absent in teleosts. Some piscine TLRs are encoded by duplicated genes, for example salmonid TLR22. TLR22 is found in several fish species but only as a non-functional pseudogene in man. Additional distinct features of the TLR pathway in bony fish suggest its specific optimization for the aquatic environment. This review summarizes studies characterizing TLRs from several teleost species and discusses features of piscine TLR signaling on the background of the respective mammalian knowledge.