In nature, destabilization of cell membranes and subsequent membrane fusion utilizes the activation of specific integral membrane proteins, termed fusogens. The primary source of information about fusogen architecture, receptor binding, and activation are from viruses. The most extensively characterized fusogens are influenza hemagglutinin (HA) and human immunodeficiency virus type 1 envelope protein (HIV-1 Env). Both fusion peptides are hydrophobic and require proteolytic cleavage, but HA is activated under acidic pH during endocytosis, while HIV-1 Env fuses at neutral pH (reviewed in [35] [36] [37] ). Less well-studied are the fusogens required for eukaryotic cell fusion such as the fusion of osteoclasts, myoblasts, and trophoblasts. The greatest challenge has been establishing which proteins are true fusogens and which proteins facilitate fusion by placing cells in close proximity. Many putative fusogens have been shown to be supporting proteins (i.e., essential for adhesion or migration). The identification of true fusogens is so difficult that groups have proposed ranking schemes to clarify the nature and function of these proteins [28] . Because putative fusogens for spontaneous stem cell fusion have not been identified, developing alternative strategies to direct stem cell fusion could augment our understanding of the biological impact of such fusion.