An egg-that took weeks to months to make in the adult-can be extraordinarily transformed within minutes during its fertilization. This review will focus on the molecular biology of the specialized secretory vesicles of fertilization, the cortical granules. We will discuss their role in the fertilization process, their contents, how they are made, and the molecular mechanisms that regulate their secretion at fertilization. This population of secretory vesicles has inherent interest for our understanding of the fertilization process. In addition, they have import because they enhance our understanding of the basic processes of secretory vesicle construction and regulation, since oocytes across species utilize this vesicle type. Here, we examine diverse animals in a comparative approach to help us understand how these vesicles function throughout phylogeny and to establish conserved themes of function.