The general mechanisms that control the cell cycle in mammalian cells have been studied in depth and several proteins that are involved in the tight regulation of cell cycle progression have been identified. However, the analysis of which molecules participate in cell cycle exit of specific cell lineages is not exhaustive yet. Moreover, the strict relation between cell cycle exit and induction of differentiation has not been fully understood and seems to depend on the cell type. Several in vivo and in vitro studies have been performed in the last few years to address these issues in cells of the nervous system. In this review, we focus our attention on cyclin–cyclin-dependent kinase complexes, cyclin kinase inhibitors, genes of the retinoblastoma family, p53 and N-Myc, and we aim to summarize the latest evidence indicating their involvement in the control of the cell cycle and induction of differentiation in different cell types of the peripheral and central nervous systems. Studies on nervous system tumors and a possible contributory role in tumorigenesis of polyomavirus T antigen are reported to point out the critical contribution of some cell cycle regulators to normal neural and glial development.