ABSTRACT: Cyclin-dependent kinases (Cdks) and their cyclin regulatory subunits control cell growth and division. Cdk2-cyclin E complexes, phosphorylating the retinoblastoma protein, drive cells through the G1/S transition into the S phase of the cell cycle. Despite its fundamental role, Cdk2 was found to be indispensable only in specific cell types due to molecular redundancies in its function. Converging studies highlight involvement of Cdk2 and associated cell cycle regulatory proteins in oligodendrocyte progenitor cell proliferation and differentiation. Giving the contribution of this immature cell type to brain plasticity and repair in the adult, this review will explore the requirement of Cdk2 for oligodendrogenesis, oligodendrocyte progenitor cells proliferation and differentiation during physiological and pathological conditions.