Due to the extreme variation in life spans among species, using a comparative approach to address fundamental questions about the aging process has much to offer. For example, maximum life span can vary by as much as several orders of magnitude among taxa. In recent years, using primary cell lines cultured from species with disparate life spans and aging rates has gained considerable momentum as a means to dissect the mechanisms underlying the variation in aging rates among animals. In this review, we reiterate the strengths of comparative cellular biogerontology, as well as provide a survey of the current state of the field. By and large this work sprang from early studies using cell lines derived from long-lived mutant mice. Specifically, they suggested that an enhanced resistance to cellular stress was strongly associated with increased longevity of select laboratory models. Since then, we and others have shown that the degree of stress resistance and species longevity is also correlated among cell lines derived from free-living populations of both mammals and birds, and more recent studies have begun to reveal the biochemical and physiological underpinnings to these differences. The continued study of cultured cell lines from vertebrates with disparate life spans is likely to provide considerable insight toward unifying mechanisms of longevity assurance.