The cell cycle is controlled by multiple mechanisms on which exogenous and endogenous stimuli converge. The pathways governing the different cell cycle phases are central for the cells' decisions when to commit to DNA synthesis and proliferation versus growth arrest, DNA repair or apoptosis. Consequently, these pathways incorporate various oncogenes and tumor suppressors and are therefore a central target for genetic alterations in human cancers. These events may ultimately lead to aberrant cell proliferation and increased genetic instability. Unraveling these regulatory networks provides an important insight into the balance of normal and cancerous cell proliferation and is pivotal for the design of novel anticancer strategies.