Mammalian life begins with a cell-cell fusion event, i.e. the fusion of the spermatozoid with the oocyte and needs further cell-cell fusion processes for the development, growth, and maintenance of tissues and organs over the whole life span. Furthermore, cellular fusion plays a role in infection, cancer, and stem cell-dependent regeneration as well as including an expanded meaning of partial cellular fusion, nanotube formation, and microparticle-cell fusion. The cellular fusion process is highly regulated by proteins which carry the information to organize and regulate membranes allowing the merge of two separate lipid bilayers into one. The regulation of this genetically and epigenetically controlled process is achieved by different kinds of signals leading to communication of fusing cells. The local cellular and extracellular environment additionally initiates specific cell signaling necessary for the induction of the cell-cell fusion process. Common motifs exist in distinct cell-cell fusion processes and their regulation. However, there is specific regulation of different cell-cell fusion processes, e.g. myoblast, placental, osteoclast, and stem cell fusion. Hence, specialized fusion events vary between cell types and species. Molecular mechanisms remain largely unknown, especially limited knowledge is present for cancer and stem cell fusion mechanisms and regulation. More research is necessary for the understanding of cellular fusion processes which can lead to development of new therapeutic strategies grounding on cellular fusion regulation.