The major economically important tick-borne diseases of cattle are theileriosis, babesiosis, anaplasmosis, and cowdriosis. Culture-derived attenuated schizonts of Theileria annulata have proved to be safe for all types of cattle and they protect against tick-borne theileriosis. T. parva was also successfully grown in vitro; however, inoculation of cattle with allogeneic schizont-infected cells resulted in rejection and destruction of the parasites together with the host cells. The number of schizont-infected cells needed for immunization is greater than for T. annulata theileriosis. Culture-propagated Babesia bovis and B. bigemina were used for large scale vaccination in the field. An avirulent population of Babesia spp. was obtained by in vitro cloning; inoculation of cattle did not induce clinical babesiosis, but produced specific antibodies. Culture-derived exoantigens of Babesia spp. proved to be completely safe for cattle, however, they conferred less protection than live parasites. Cell-cultured Cowdria ruminantium was highly infective for susceptible animals but, attenuated in vitro, could offer a potential source for vaccination. Anaplasma marginale, successfully grown in tick cell culture, may be developed for vaccines. Factors that should be considered in the developing of vaccines against tick-borne diseases include: the protective immune response to the pathogenic parasite developmental stages, virulence, immunological strain differences, and antigenic variations in cattle and in culture.