Cancer is a disease of uncontrolled cell proliferation. The cell cycle provides a crucial platform for coordination between proliferation and cell death. Somatic cells undergo replication and division by traversing the tightly regulated cell cycle. Growth factors play a critical role in initiating signaling events stimulating cell cycle progression, which is crucial for their mitogenic and tumorigenic effects. Epidermal growth factor receptor (EGFR) and its ligands are frequently upregulated in human cancers. The oncogenic effects of EGFR include initiation of DNA synthesis, enhanced cell growth, invasion, and metastasis. Specific abrogation of EGFR results in cell cycle arrest, apoptosis, or dedifferentiaton of cancer cells. Downregulation of EGFR signaling has therapeutic benefit in preclinical and clinical studies. Therefore, better understanding of the mechanisms of regulation and coordination between the cell cycle, cell growth, and cell death will lead to the development of novel cancer therapies.