Irrespective of body size and phylogenetic diversity, the skeletal systems of terrestrial mammals are built of tissue components having similar mechanical properties and material organization. Because of scale effects on skeletal form, therefore, larger mammals increase the effective mechanical advantage of their limbs to decrease mass-specific forces associated with the support of gravitational loads imposed during locomotion to maintain a similar safety factor. Larger animals accomplish this by adopting a more upright posture while running, which aligns their limb joints more closely with the resultant ground reaction force, thereby decreasing the mass-specific force that their muscles must generate to support externally applied joint moments. As a result, peak (compressive) bone stresses determined from in vivo bone strain recordings and force platform and kinematic analyses of the limb generally range from −40 to −80 MPa (mean:​ −55 ± 23 MPa), corresponding to a safety factor to compressive bone failure of about three to four. The decrease in mass-specific muscle force indicates that the maximum stresses developed in limb muscles of different sized species are also similar at equivalent levels of performance. Stresses developed in the midshafts of most long bones are primarily the result of bending, often engendered by axial forces transmitted about the bone's longitudinal curvature. The consistency of bending-induced skeletal strain over a range of physical activity and the associated expense of increased strain magnitude that this form of loading incurs suggest that functional strain patterns developed through bending may be a desirable architectural objective of most long bones. Alteration of a bone's normal functional strain distribution, therefore, is likely a key factor underlying adaptive remodeling in response to changes in mechanical loading.