Publisher Summary This chapter provides an overview of fertilization—a process by which haploid gametes, sperm and egg, unite to produce a genetically distinct individual. Oocytes acquire full ability to activate just prior to ovulation. Gonadotropin-stimulated antral follicles have preovulatory oocytes that are fully grown, but unable to undergo normal activation if retrieved and injected with inositol-1,4,5-trisphosphate (IP3) or fertilized in vitro. Although the most obvious sign of immaturity is their stage of meiotic maturation, the stage of the oocyte chromatin does not actually explain the failure of normal activation. Important changes in the mammalian oocyte cytoplasm take place during luteinizing hormone (LH)-induced meiotic maturation and are likely to be responsible for the development of activation competence. Like uncapacitated sperm, pre-ovulatory oocytes do not undergo normal signaling and secretion. In addition, fertilized pre-ovulatory oocytes are not able to induce normal decondensation of the sperm chromatin, convert it into a functional state, and undergo pronuclear envelop formation. Translationally mediated increases in expression of proteins such as IP3 receptor (IP3R), glutathione, and calmodulin-dependent protein kinase II (CaMKII), as well as several crucial cell cycle kinases are considered to be important for normal egg activation and onset of development.