Progression of the cell cycle in mammalian cells, as in all other organisms, is associated with the phase-specific transcription of defined sets of genes. Such periodically expressed genes frequently encode proteins that either directly control cell-cycle progression or function in metabolic processes linked to the cell cycle, such as nucleotide and DNA biosynthesis. Here, I summarize our current knowledge and views of the mechanisms governing the coupling of cell-cycle control mechanisms to transcriptional regulation, with particular emphasis on the transcription factor E2F and its connections with cyclin-dependent kinases and the retinoblastoma gene family.