The E2F family of transcription factors plays a pivotal role in the regulation of cell proliferation and their activity is often deregulated in human tumors. Recent studies demonstrate that E2F1 can induce both proliferation and apoptosis. E2F1-induced apoptosis occurs via multiple pathways, some of which induce stabilization and activation of the tumor suppressor p53. The pro-apoptotic activity of E2F1 suggests that its deregulation constitutes an oncogenic stress that may target pre-malignant cells to undergo apoptosis, thus preventing tumor development.