Over the last decades, it has become clear that glia are multifunctional and plastic cells endowed with key regulatory roles. They control the response to developmental and/or pathological signals, thereby affecting neural proliferation, remodeling, survival, and regeneration. It is, therefore, important to understand the biology of these cells and the molecular mechanisms controlling their development/activity. The fly community has made major breakthroughs by characterizing the bases of gliogenesis and function. Here we describe the regulation and the role of the fly glial determinant. Then, we discuss the impact of the determinant in cell plasticity and differentiation. Finally, we address the conservation of this pathway across evolution.