The review by Reinhard Jahn and Dirk Fasshauer discusses the molecular mechanisms governing exocytosis of synaptic vesicles, focusing on the key proteins involved and the biochemical and biophysical processes that occur. The authors highlight the roles of SNARE proteins (such as synaptobrevin, syntaxin, and SNAP-25), synaptotagmins, complexins, Munc18, and Munc13 in the exocytotic process. They explain how these proteins facilitate vesicle docking, priming, and calcium-dependent triggering of membrane fusion. Despite significant progress, there are still gaps in understanding the precise molecular sequence of events from vesicle docking to calcium-triggered membrane fusion. The review also explores the structural and functional properties of these proteins, the challenges in assigning specific functions to individual proteins, and the complex interplay between proteins and lipids during fusion. The authors propose an alternative model for the docked and primed state of synaptic vesicles, suggesting that SNAREs do not fully zipper before calcium arrival, and discuss the implications for the efficiency and cooperativity of calcium-triggered fusion. Finally, they emphasize the importance of recent advances in technologies such as super-resolution microscopy and cryo-electron tomography in advancing our understanding of the exocytotic process.The review by Reinhard Jahn and Dirk Fasshauer discusses the molecular mechanisms governing exocytosis of synaptic vesicles, focusing on the key proteins involved and the biochemical and biophysical processes that occur. The authors highlight the roles of SNARE proteins (such as synaptobrevin, syntaxin, and SNAP-25), synaptotagmins, complexins, Munc18, and Munc13 in the exocytotic process. They explain how these proteins facilitate vesicle docking, priming, and calcium-dependent triggering of membrane fusion. Despite significant progress, there are still gaps in understanding the precise molecular sequence of events from vesicle docking to calcium-triggered membrane fusion. The review also explores the structural and functional properties of these proteins, the challenges in assigning specific functions to individual proteins, and the complex interplay between proteins and lipids during fusion. The authors propose an alternative model for the docked and primed state of synaptic vesicles, suggesting that SNAREs do not fully zipper before calcium arrival, and discuss the implications for the efficiency and cooperativity of calcium-triggered fusion. Finally, they emphasize the importance of recent advances in technologies such as super-resolution microscopy and cryo-electron tomography in advancing our understanding of the exocytotic process.