The ability to stimulate the immune response of cattle and pigs offers a new means of disease intervention. This review discusses current in vivo experiments that have evaluated immunomodulators in cattle and pigs. Levamisole, thiabendazole, imuthiol, avridine, isoprinosine, bovine recombinant interferon, human recombinant interleukin-2, bovine recombinant interleukin-2 and various supplemental vitamins and minerals have been used as immunomodulators in livestock with various degrees of success. Future research on immunomodulators, specific for domestic farm animals, will provide additional methods of treating immunosuppressed animals.