Over the past decade, studies focusing on the mechanisms controlling cellular proliferation have converged with equally intensive efforts directed at the analysis of oncogenic pathways associated with human cancer. These convergent studies have revealed the central role played by the pathway that controls the activity of the retinoblastoma tumor suppressor protein (Rb), which in turn regulates the E2F transcription factor. In particular, it is now clear that the Rb/E2F pathway is critical in regulating the initiation of DNA replication. It is also clear that the control of the pathway is disrupted in virtually all human cancers. Questions remain, however, as to the specific role played by individual activities within the pathway in the control of cell growth and their participation in the development of cancer.