The skeleton fulfills its mechanical functions through structural organization and material properties of individual bones. It is stated that both cortical and trabecular morphology and mass can be (re)modeled in response to changes in mechanical strains engendered by load-bearing. To address this, animal models that enable the application of specific loads to individual bones have been developed. These are useful in defining how loading modulates (re)modeling and allow examination of the mechanisms that coordinate these events. This chapter describes how to apply mechanical loading to murine bones through points of articulation, which allows changes in endosteal, periosteal as well as trabecular bone to be revealed at multiple hierarchies, by a host of methodologies, including double fluorochrome labeling and computed tomography. In some instances, we consider how loads can be applied in order to allow responses in other components of the skeletal system to be examined.