As donor organs and tissues for transplantation medicine are scarce, alternative methods for replacing damaged cells or restoring organ function are highly needed. Here, we consider the therapeutic potential of cell fusion. After highlighting the various contexts in which cells are known to fuse during mammalian development, we discuss the implications of the observation that cell fusion can occur with restorative effects following tissue damage or cell transplantation. There are still, however, many challenges facing those who wish to implement cell fusion as a therapeutic tool. These include identifying the best cells to use for reparative fusion, determining the best route of introducing these cells into the desired tissue, discovering methods to increase the incidence of cell fusion, and ensuring the functionality of the resulting fusion products. If these difficulties can be overcome, cell fusion might have therapeutic potential as highlighted by several recent transplantation studies.