Implantation is a vital phase in pregnancy whereupon the hatched embryo invades into the uterine wall to establish intimate contacts with the mother for further development. Although it is generally believed that proteinases are major factors that confer the embryo its invasive character, the nature of proteinases involved in implantation remain mostly elusive. In this article, we review the organization, structure and postulated function of the implantation serine proteinase (ISP1 and 2) genes. The ISPs are embedded within a cluster of tryptase genes on mouse chromosome 17. They are most closely related to members of the mast cell tryptase family, indicating that they may possess some properties characteristic of tryptases including multimerization-dependent activation. The significant similarities found in regulatory regions of ISP genes, together with the observation that ISP proteins are co-expressed and heterodimerize in the embryo and uterus suggests that they are intimately co-regulated during implantation. Inhibition of ISP proteolytic function has implicated this enzyme in the processes of embryo hatching and implantation.