Fertilized eggs and early blastomeres, that have the potential to develop to fetuses when placed into a uterus, are totipotent. Those cells in the embryo, that can give rise to all cell types of an organism, but not to an organism itself, are pluripotent. Embryonic stem (ES), embryonic carcinoma (EC), and embryonic germ (EG) cells are powerful in vitro artifacts derived from different embryonic stages and are pluripotent. Totipotent and pluripotent cells have the potential to greatly benefit biological research and medicine. One powerful feature is that the genetic program of somatic cells can be converted into that of totipotent or pluripotent cells, as shown by nuclear transfer or cell fusion experiments. During reprogramming by cell fusion various features of pluripotent cells are acquired. These include the typical morphology of the respective pluripotent fusion partner, a specific epigenetic state, a specific gene profile, inactivation of tissue-specific genes expressed in the somatic fusion partner, and the developmental as well as differentiation potential of pluripotent cells. In this review, we will discuss what is known about the reprogramming process mediated by cell fusion and the potential use of fusion-induced reprogramming for therapeutic applications.