The article by Chernomordik and Kozlov explores the mechanics of membrane fusion, focusing on the structures and energies of fusion intermediates in protein-free lipid bilayers. They identify two key intermediates: hemifusion structures, where the outer leaflets of apposed membranes mix without content mixing, and fusion pores, which involve both outer and inner leaflets. The formation of these intermediates is influenced by lipid composition, particularly the spontaneous curvature of lipids, and the establishment of close inter-bilayer contact. The authors discuss the role of protein-generated membrane stresses in driving the progression from close juxtaposition of membrane bilayers to the expansion of a fusion pore. They propose that the entire process is controlled by protein-generated membrane stresses, which can be transmitted through transmembrane domains and fusion peptides. The article also reviews the conserved fusion-through-hemifusion pathway observed in various biological fusion reactions, including cell-to-cell fusion, viral entry, and intracellular fusion. The authors highlight the importance of understanding the molecular mechanisms of membrane fusion for controlling this ubiquitous phenomenon.The article by Chernomordik and Kozlov explores the mechanics of membrane fusion, focusing on the structures and energies of fusion intermediates in protein-free lipid bilayers. They identify two key intermediates: hemifusion structures, where the outer leaflets of apposed membranes mix without content mixing, and fusion pores, which involve both outer and inner leaflets. The formation of these intermediates is influenced by lipid composition, particularly the spontaneous curvature of lipids, and the establishment of close inter-bilayer contact. The authors discuss the role of protein-generated membrane stresses in driving the progression from close juxtaposition of membrane bilayers to the expansion of a fusion pore. They propose that the entire process is controlled by protein-generated membrane stresses, which can be transmitted through transmembrane domains and fusion peptides. The article also reviews the conserved fusion-through-hemifusion pathway observed in various biological fusion reactions, including cell-to-cell fusion, viral entry, and intracellular fusion. The authors highlight the importance of understanding the molecular mechanisms of membrane fusion for controlling this ubiquitous phenomenon.