Uncontrolled proliferation is a hallmark of cancer cells. Molecular analysis of human tumors and animal models have provided a clear basis for the understanding of the cellular processes that govern cell cycle progression in normal and tumor cells. Many cell cycle regulators controlling the correct entry and progression through the cell cycle are altered in tumors. In fact, most, if not all, human cancers show a deregulated control of G1 progression, a period when cells decide whether to start proliferation or to stay quiescent. In addition, tumor cells have impaired cell cycle checkpoints, resulting in the accumulation of genetic aberrations. Manipulation of these control mechanisms provides new avenues for the design of advanced therapeutic strategies against tumor development.