In mammals, two integral membrane proteins, sperm IZUMO1 and egg CD9, regulate sperm-egg fusion, and their roles are critical, but yet unclear. Recent studies, however, indicate interesting connections between the sperm-egg fusion and virus-induced cell-cell fusion. First, CD9-containing exosome-like vesicles, which are released from wild-type eggs, can induce the fusion between sperm and CD9-deficient egg, even though CD9-deficient eggs are highly refractory to the fusion with sperm. This finding provides strong evidence for the involvement of CD9-containing, fusion-facilitating vesicles in the sperm-egg fusion. Secondly, there are similarities between the generation of retroviruses in the host cells and the formation of small cellular vesicles, termed exosomes, in mammalian cells. The exosomes are involved in intercellular communication through transfer of proteins and ribonucleic acids (RNAs) including mRNAs and microRNAs. These collective studies provide an insight into the molecular mechanism of membrane fusion events.