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Clinical Forriol, Francisco MD, PHD *; Shapiro, Frederic MD +++ Abstract: A deeper understanding of skeletal development comes from knowledge of the molecular components, cell and tissue structure, and biophysical and vascular mechanisms underlying physiologic function. Endochondral and intramembranous bone formation mechanisms are active during long bone synthesis. Most endochondral growth in length occurs at the physes by the coordinated actions of cell proliferation, matrix synthesis, and chondrocyte hypertrophy. Several intrinsic molecules act to modulate physeal structure and function whereas extrinsic molecules, such as hormones, provide systemic regulation of growth. Biophysical forces develop intrinsically within the growing bone, serving to enlarge it in three dimensions, while extrinsic forces resist and channel expansion into normal recognizable and functional forms. Newer imaging modalities, such as magnetic resonance imaging, are highly effective in assessing epiphyseal vascularity and differentiating fibrous, cartilaginous, mineralized and osseous tissues in prenatal and postnatal developing bone. This study illustrates the interplay between the molecular and biophysical aspects of normal bone growth, shows ways in which altered development leads to abnormal structures, and provides examples where biologic and biophysical interventions can affect bone development in favorable ways.