The mammalian zona pellucida (ZP) is an extracellular matrix that surrounds ovarian oocytes, ovulated eggs, and preimplantation embryos, and it plays several important roles at different stages of reproduction. Newly developed technologies such as transgenic mouse production, database analysis of signal networks, and live-cell imaging have revealed novel findings about the ZP and fertilization. Assisted reproductive technology has also provided new insights into human ZP morphology and function. Recent micromanipulation technologies such as intracytoplasmic sperm injection, are very helpful for treatment of ZP-related infertility. This article describes the current understanding of the following aspects of the mammalian ZP: I) ZP structure, II) ZP functions, III) ZP-related infertility and IV) ZP-based immunocontraceptive vaccines.