A prevailing assumption in the cardiovascular field is that the metabolic rate of the heart is a constant proportion of a mammal's whole-body aerobic metabolic rate. In this Commentary, we assemble previously published cardiovascular, metabolic and body mass data from matched terrestrial mammalian species, at rest and during heavy exercise, and reveal scaling relationships that challenge this assumption. Our analyses indicate that the fractional metabolic cost of systemic perfusion compared with whole-body metabolic rate increases significantly with body size among resting mammals, from ∼2.5% in a mouse to ∼10% in an elephant. We propose that two significant body size-dependent effects contribute to this conclusion; namely, that larger species generate higher mean systemic arterial blood pressure and that their myocardium operates with lower external mechanical efficiencies compared with those of smaller species. We discuss potential physiological and mechanical explanations, including the additional energy needed to support the arterial blood column above the heart in larger species, especially those with long necks, as well as the possible sources of greater internal energy losses from the heart of larger species. Thus, we present an updated view of how increasing blood pressure and decreasing efficiency of the myocardium result in an increasing fractional metabolic cost of perfusion as body size increases among resting mammals.