Advanced age is an independent risk factor for natural death and common diseases, such as cardiovascular diseases, dementia, and cancers, which are life-threatening and cause disabilities. On the other hand, individual with healthy longevity is a plausible model for successful aging. Thus, search for longevity-associated genes and pathways likely provides a unique approach to understand the genetic mechanisms underlying aging and healthspan, and emerging evidence from model organisms has highlighted the significance of genetic components in longevity. Here we reviewed the uses of model organisms including yeast, ciliate, nematode, arthropod, fish, rodent, and primate as well as human to identify the genetic determinants of longevity and discussed the genetic contributions of conserved longevity pathways, such as adrenergic system, AMPK, insulin/IGF-1, and mTOR signaling pathways.