During locomotion and exercise, bone is subjected to forces induced by gravitational loading and muscle loading. The inherent link between these modes of loading has confounded emergence of either one as the principal anabolic or anticatabolic signal in bone. A paradigm has emerged in the literature stipulating that muscle loading is the larger of the two, and therefore, bone morphology is predominantly determined by muscle loads. In spite of the intuitive appeal of a muscle-bone unit tuned to the magnitude of contractile forces, little evidence exists for the relatively few, large-magnitude muscle contractions arising during daily activities to dominate the mechanosensory input of bone. Moreover, a review of the literature raises several inconsistencies in this paradigm and indicates that the alternative-gravitational loading-can have a significant role in determining bone mass and morphology. Certainly, the relative contribution of each type of loading will depend on the specific activity, the location of the bone within the skeleton, and whether the bone is weight-bearing or not. Most likely, a more comprehensive paradigm for explaining sensitivity of bone to loading will have to include not only large-magnitude gravitational and muscle loads, but also other factors such as high-frequency, low-magnitude signals generated by the muscles during postural adjustments.