Major advances in aging research have been made by studying the effect of genetic modifications on the lifespan of organisms, such as yeast, invertebrates (worms and flies) and mice. Data from yeast and invertebrates have been the most plentiful because of the ease in which genetic manipulations can be made and the rapidity by which lifespan experiments can be performed. With the ultimate focus on advancing human health, testing genetic interventions in mammals is crucial, and the mouse has proven to be the mammal most amenable to this task. Lifespan studies in mice are resource intensive, requiring up to 4 years to complete. Therefore, it is critical that a set of scientifically-based criteria be followed to assure reliable results and establish statistically significant findings so other laboratories can replicate and build on the data. Only then will it be possible to confidently determine that the genetic modification extends lifespan and alters aging.