The reason why metabolic rate often scales allometrically (disproportionately) with body mass has been debated for decades. A critical question concerns whether metabolic scaling is controlled intrinsically at the intracellular level or systemically at the organismal level. Recently, the relative importance of these effects has been tested by examining the metabolic rates of cultured dermal fibroblast and skeletal muscle cells in relation to donor body mass of a variety of birds and mammals. The lack of a relationship between in vitro cellular metabolic rates and body mass suggests that systemic effects, not intrinsic cellular effects are responsible for allometric metabolic scaling observed in whole organisms. Influential resource-transport network theory claims that the most important systemic effect involved is body-size related resource-supply limits to metabolizing cells. However, comparisons of in vitro cellular metabolic rates with scaling relationships for in vivo (basal) metabolic rates suggest that other systemic effects, such as body-size dependent biological regulation and tissue composition may also have major, perhaps more important effects. Furthermore, systemic effects must ultimately act at the cellular level, for example, by induced variation in the function, structure and intracellular densities of mitochondria. The mechanistic pathways involved require further study.