Toll-like receptors (TLRs) are the most famous pattern-recognition receptors (PRRs); they monitor pathogen-associated molecular patterns and play a critical role in activation of the immune system against infection. TLR gene mutations may affect the gene products in terms of their ligand-binding ability or their signal transduction ability after ligand binding; such changes have a great influence on pathogen monitoring and disease resistance. Thirteen mammalian TLRs have been identified, and genes corresponding to all 10 TLR genes identified in humans have been fully cloned in pigs. Porcine TLR gene coding sequences possess a large number of nonsynonymous single nucleotide polymorphisms (SNPs). They are concentrated in ectodomains, and may increase the variability of pathogen recognition in pig populations. We summarize the current knowledge of TLR molecules in mammals and livestock (particularly pigs) and speculate on the relationship between SNPs in porcine TLRs and their application to vaccine design and disease-resistance breeding.