Cancers arise in a tissue as the culmination of a series of mutations that activate oncogenes and inactivate tumor suppressor genes. Many of these mutations affect cell proliferation and survival. Recently, it has become apparent that some oncogenes and tumor suppressor genes also regulate self-renewal, the process by which stem cells maintain themselves. In some cancer cells, the process of self-renewal is de-regulated resulting in expansion of these cells and tumors. It is likely that targeting cancer cell self-renewal pathways will result in more effective cancer therapies.