Although all functional movement arises from the interplay between the neurological, skeletal, and muscular systems, it is the skeletal system that forms the basic framework for functional movement. Central to understanding human neuromuscular development, along with the genesis of musculoskeletal pathologies, is quantifying how the human skeletal system adapts and mal-adapts to its mechanical environment. Advancing this understanding is hampered by an inability to directly and non-invasively measure in vivo strains, stresses, and forces on bone. Thus, we traditionally have turned to animal models to garner such information. These models enable direct in vivo measures that are not available for human subjects, providing information in regards to both skeletal adaptation and the interplay between the skeletal and muscular systems. Recently, there has been an explosion of new imaging and modeling techniques providing non-invasive, in vivo measures and estimates of skeletal form and function that have long been missing. Combining multiple modalities and techniques has proven to be one of our most valuable resources in enhancing our understanding of the form-function relationship of the human skeletal, muscular, and neurological systems. Thus, to continue advancing our knowledge of the structural-functional relationship, validation of current tools is needed, while development is required to limit the deficiencies in these tools and develop new ones.