Lactoferrin (Lf) is an iron-chelating glycoprotein present in milk and mucosal secretions, a component of the mammalian innate immune system. Lf is microbiostatic and microbicidal. Lf can reduce the bacterial expression of virulence factors, such as those involved in biofilm production and protease secretion. The high identity among mammalian Lf sequences facilitates its use in human and veterinary medicine. Lf of bovine origin is the principal Lf used due to its commercial availability through purification from milk whey; recombinant Lfs (bovine, human, and porcine) have been used as well. Lf is a stable protein that retains its physicochemical characteristics under gastric pH conditions, and in most cases it is bioactive even after digestion; thus, the incorporation of Lf into diets facilitates its administration to animals. The aim of this review is to examine original research in which the effects of bovine and porcine Lf on pathogens of domestic animals have been demonstrated through in vitro and in vivo assays, with the purpose of ascertaining the benefits that Lf provides in the treatment of infectious diseases.