Most readers of this review originated from a sperm-egg fusion event. Cell fusion is a process that is crucial at many intersections later during development. However, we do not know which molecules (fusogens) fuse the membranes of gametes to form zygotes, myoblasts to form myotubes in muscles, macrophages to form osteoclasts in bones, or cytotrophoblasts to form syncytiotrophoblasts in placentas. There are five gold standards that can be applied for the identification of genuine fusogens. Based on these criteria, a numerical score can be used to assess the likelihood of protein fusogenicity. We compare distinct families of candidate developmental, viral and intracellular fusogens and analyze current models of membrane fusion.