Ticks are economically important ectoparasites of domestic and wild animals and are considered to be second worldwide to mosquitoes as vectors of human pathogens. Current control methods for ticks, based primarily on the use of acaricides, have had limited efficacy in the reduction of tick infestations and the use of acaricides is often accompanied by serious drawbacks, including selection of acaricide-resistant ticks and environmental contamination. Development of improved vaccines against tick infestations offers a cost-effective and environmentally sound control method. Commercial vaccines currently marketed for control of cattle ticks have been effective in field studies when used in concert with integrated control strategies. However, new antigens are needed to increase the efficacy of tick vaccines. Although a limited number of protective antigens against tick infestations have been identified and characterized, discovery of new antigens remains the limiting step for improving the efficacy of tick vaccines. Recent technologies developed for gene discovery, including expression library immunization and evaluation of expressed sequence tags, show promise for rapid, systematic and global antigen screening and should provide a comprehensive approach to selection of candidate vaccine antigens. Design of future tick vaccines should target multiple tick species, as well as interfere with the transmission of pathogens.