Toll-like receptors (TLRs) arc a family of evolutionarily conserved, integral membrane glycoproteins that play a key role in innate immunity through the early sensing of pathogens and the initiation of appropriate responses. Each TLR receptor recognizes conserved motifs in macromolecular components from viruses and bacteria; the expression of the TLRs in cells and tissues therefore provide specific responses to pathogenic challenges. TLR activation addresses and reinforces both arms of the immune response (innate and adaptive), leading to prompt and specific activities toward pathogens. Although best studied in mouse and human genomes, orthologous TLRs have been identified in other vertebrates, including fish. Because of their early function of controlling immunity in animal species, TLR genes can be considered traits conferring disease resistance and should be considered suitable targets in the development of innovative immunotherapeutic. In the present review, the current knowledge on TLR receptors in domestic animal species is summarized and discussed from the point of view of the host-pathogen interaction.