In Drosophila, as in mammals, myoblast fusion is fundamental for development. This fusion process has two distinct phases that share common ultrastructural features and at least some molecular players between Drosophila and vertebrates. Here, we integrate the latest data on the key molecular players and ultrastructural features found during myoblast fusion into a new working model to explain this fundamental cellular process. At cell-cell contact sites, a protein complex (FuRMAS) serves as a signalling centre and might restrict the area of membrane fusion. The FuRMAS consists of a ring of cell adhesion molecules, signalling proteins, and F-actin. Regulated F-actin branching plays a pivotal role in myoblast fusion with regard to vesicle transport, fusion pore formation, and expansion as well as the integration of the fusion-competent myoblast into the growing myotube. Interestingly, local F-actin accumulation is a typical feature of other transient adhesive structures such as the immunological synapse, podosomes, and invadopodia. Developmental Dynamics 238:1513-1525, 2009. (c) 2009 Wiley-Liss, Inc.