oncogenic drivers, are common in tissues starting at a young age. These observations raise the question: how do we largely avoid cancer for most of our lives? Here we propose that evolutionary forces can help explain this paradox. As humans and other organisms age or experience external insults such as radiation or smoking, the structure and function of tissues progressively degrade, resulting in altered stem cell niche microenvironments. As tissue integrity declines, it becomes less capable of supporting and maintaining resident stem cells. These stem cells then find themselves in a microenvironment to which they are poorly adapted, An evolutionary perspective on cancer must integrate these processes of natural and oncogenic selection. Acting on the genetic make-up of multicellular organisms, natural selection has generated barriers to cancer, which we define as mechanisms that block progression to cancer. Current knowledge allows five categories of adaptations to be classified as barriers to metastatic cancer: cell cycle arrest, apoptosis, caps on the total number of future cell divisions, cell adhesion, and asymmetric cell division (i.e., a stem cell division that generates one stem cell and one cell destined to differentiate during subsequent proliferation). We distinguish such barriers from restraints, which slow or inhibit the progression to cancer. An example of a restraint is the regulation of the rate of division of a dividing cell. This restraint does not prevent cancer, but it may retard oncogenesis and generate a cancer cell .