Immunological protection of hosts against tick infestation is at present the most practically sustainable alternative tick control method to the current use of acaricides that is riddled with serious limitations. The current focus of tick vaccine research is the identification, cloning and in vitro production of recombinant tick vaccine candidate antigens. We have examined a selected number of reports on the roles of parasite-encoded members of the serine proteinase inhibitor (serpin) superfamily in modulation of mammalian anti-parasite defense and developed some food for thought commentaries on the possibility of targeting this class of proteins for anti-tick vaccine development.