The zona pellucida is surrounding the oocyte and the early developing embryo. It serves several functions, from ovulation until shortly before implantation. Initially it induces sperm-oocyte interaction, acrosom-reaction and prevents polyspermy. Later, it prevents disaggregation of the non-compacted blastomeres and the premature attachment to the oviductal and endometrial surface. Additional, it protects the embryo against toxins and antibiotics, as well as bacteria, viruses and phagocytes. As the embryo is covered by the zona pellucida until immediately before implantation, all signals of the embryo-maternal signalling have to pass the zona and are detectable within it. Logically we may define the zona pellucida as a mailbox of the embryo-maternal signalling. Oviductal, uterine and embryonic proteins are incorporated into the zona pellucida as embryonic development goes on and change the zona's morphological and biochemical properties. Whether a protein is able to penetrate the zona, whether it accumulates within the zona or whether it is rejected by the zona depends on its biochemical properties and can be predicted by its Van der Waals attraction and by either the hydro- or lipophily. New cognitions in the physiology of the zona pellucida might lead to new achievements of the in-vitro culture of embryos, and present new aspects how to prevent zona hardening. Furthermore, the knowledge of the zona proteins enables the development of immunocontraceptive-vaccines. Consequently, the zona pellucida is not only significant with regard to fertilisation, but also during early embryonic development. Investigations of the zona pellucida will yield new insights into early embryo-maternal signalling which in turn may lead to improvements of classic IVF and new approaches of in-vitro culture.