The positive interspecific relation between mammalian body size and longevity was described more than a century ago and remains one of the most robust patterns known in the biology of aging. Hypotheses about the role of metabolic rate or relative brain size in explaining this pattern have not been supported by detailed analyses. This pattern may be due to an inverse relation between mitochondrial oxygen radical production and body size, although evidence for this hypothesis is sparse. On a less mechanistic level, evolutionary senescence theory provides a compelling rationale that species regardless of size that are less prone to environmental hazards evolve longevity assurance mechanisms leading to longer life-and health span. Considerable evidence suggests that the opposite pattern -smaller size associated with longer life -obtains within species, although detailed information is available for only a few species. Within the species -mice, dogs, and horses -in which this relationship is well-established, the deleterious effects of growth hormone acting either autonomously or through its effect on IGF-I signaling provide a possible explanatory mechanism. Evidence from humans does not appear to conform to this pattern, perhaps because of the dominance of cardiovascular disease as a human cause-of-death. © 2010 Springer Science+Business Media B.V.