ABSTRACTIn sexually reproducing organisms, the genetic information is transmitted from one generation to the next via the merger of male and female gametes. Gamete fusion is a two-step process involving membrane recognition and apposition through ligand–receptor interactions and lipid mixing mediated by fusion proteins. HAP2 (also known as GCS1) is a bona fide gamete fusogen in flowering plants and protists. In vertebrates, a multitude of surface proteins have been demonstrated to be pivotal for sperm–egg fusion, yet none of them exhibit typical fusogenic features. In this Cell Science at a Glance article and the accompanying poster, we summarize recent advances in the mechanistic understanding of gamete fusion in eukaryotes, with a particular focus on mammalian species.