Lifespan experiments of lower organisms and mammals along with recent studies of centenarians are making inroads into delineating genetic factors that determine the ability to achieve exceptional longevity. These models may be helpful for the discovery of both longevity-enabling genes as well as genes associated with increased propensity to develop specific diseases. Both academic and commercial laboratories are putting substantial resources into discovering such genes in order to better understand the genetic and environmental underpinnings of how some people age more slowly than others and markedly delay or even escape age-associated diseases.