Somatic cells can be reprogrammed into a pluripotent cellular state similar to that of embryonic stem cells. Given the significant physiological differences between the somatic and pluripotent cells, cell reprogramming is associated with a profound reorganization of the somatic phenotype at all levels. The remodeling of mitochondrial morphology is one of these dramatic changes that somatic cells have to undertake during cell reprogramming. Somatic cells transform their tubular and interconnected mitochondrial network to the fragmented and isolated organelles found in pluripotent stem cells early during cell reprogramming. Accordingly, mitochondrial fission, the process whereby the mitochondria divide, plays an important role in the cell reprogramming process. Here, we present an overview of the importance of mitochondrial fission in both cell reprogramming and cellular transformation.