Animal life-history traits fall within a limited ecological space, a continuum referred to as a "slow-fast" life-history axis. Differences of life-history traits are thought to result from trade-offs between behavioral and physiological aspects in each species as mediated by the biotic and abiotic environment, as well as genetic mechanisms. Domestic animals tend to show inverse relationships between body size and life span. Dogs are a good example of this, with smaller dogs having higher mass-specific metabolic rates and longer lifespans compared with larger dogs. Thus, dogs provide a unique system to examine physiological consequences of life-history trade-offs. I have collected data from the literature to explore implications of these trade-offs at several levels of physiological organization including whole-animal, organ systems, and cells. Small dogs tend to have longer lifespans, fewer pups per litter, faster and shorter developmental trajectories, and higher mass-specific metabolic rates, and in general, larger metabolically active organs compared with large dogs. From work on isolated primary fibroblast cells and telomeres of dogs, I show that selection for body size may influence the attributes of cells that shape proliferative cellular rates and rates of telomere shortening. The potential links between body size, and cellular oxidative stress in dogs as they age are discussed. Furthermore, small size in dogs has been linked to concentrations of reduced insulin growth factor-1 (IGF-1) levels in plasma, a possible metabolic advantage that may provide higher resistance to oxidative stress, a parameter essential to increases in lifespan.