Membrane fusion is an ubiquitous event in cell biology. One can distinguish two types of fusion: (i) outside/outside fusion, for example endocytosis, and (ii) inside/inside fusion, for example exocytosis. In spite of this difference in types of fusion in relation to membrane asymmetry and in spite of the large variety of lipid compositions encountered in biological membranes, a universal mechanism can be postulated for the role of lipids in membrane fusion. In this concept the lipids leave the bilayer configuration temporarily and locally. This notion, and the fact that any biological membrane contains a substantial amount of lipids which prefer the non-bilayer hexagonal II phase in physiological conditions, has led to the hypothesis that such hexagonal II phase lipids play a crucial role in membrane fusion. This proposition is strongly supported by model membrane experiments in which it has been demonstrated that factors such as Ca2+ and temperature, which trigger the transition from bilayer to hexagonal II phase, in fact induce membrane fusion.