Oligodendrocyte Progenitor Cells (OPCs) first appear at mid embryogenic stages during development of the mammalian CNS and a mitotically active population of them remains present even into late adulthood. During the life-time of the organism they initially proliferate and migrate in order to populate the whole nervous tissue, then they massively generate oligodendrocytesand finally they switch to a less mitotically active phase generating new oligodendrocytes at a slow rate in the adult brain; importantly, they can regenerate acutely or chronically destroyed myelin. All the above depend on the capacity of OPCs to regulate their cell cycle within different contexts. In this review we describe the development of OPCs, their differential mitotic behavior in various conditions (embryo, disease, ageing), we discuss what is known about the mechanisms that control their cell cycle and wehighlightfew interesting and still open questions.