E2F transcription factor 2 (E2F2) is a member of the E2F family of transcription factors. The classical view is that some E2Fs act as "activators" and others "inhibitors" of cell cycle gene expression. However, the so-called "activator" E2F2 is particularly enigmatic, with seemingly contradictory roles in the cell cycle, proliferation, apoptosis, inflammation, and cell migration and invasion. How can we rationalize the apparently opposing functions of E2F2 in different situations? This is difficult because different methods of studying E2F2 have yielded conflicting results, so extrapolating mechanisms from an observed endpoint is challenging. This review will attempt to summarize and clarify these issues. This review focuses on genetic studies that have helped elucidate the biological functions of E2F2 and that have enhanced our understanding of how E2F2 is integrated into pathways controlling the cell cycle, proliferation, apoptosis, inflammation, and cell migration and invasion. This review will also discuss the function of E2F2 in cancer and other diseases. This review provides a strong basis for further research on the biological function and clinical potential of E2F2.