The ability to maintain cells in a differentiated state and to prevent them from reprogramming into a multipotent state has recently emerged as a central theme in neural development as well as in oncogenesis. In the developing central nervous system (CNS) of the fruit fly Drosophila, several transcription factors were recently identified to be required in postmitotic cells to maintain differentiation, and in their absence, mature neurons undergo dedifferentiation, giving rise to proliferative neural stem cells and ultimately to tumor growth. In this review, we will highlight the current understanding of dedifferentiation and cell plasticity in the Drosophila CNS.