The E2F transcription factors are critical regulators of genes required for appropriate progression through the cell cycle, and in special circumstances they can also promote the expression of another class of genes that function in the apoptotic program. Since E2Fs can initiate both cell proliferation and cell death, it is not surprising that the pro-apoptotic capacity of these proteins is subject to complex regulation. Recent study has expanded our knowledge of the factors influencing E2F-induced apoptosis as well as downstream targets of E2F in this process.