This chapter reviews the biochemical, hormonal, and hematological factors in the onset and development of adolescent idiopathic scoliosis (AIS), an orthopedic entity of unknown etiology. Briefly, AIS is defined as a lateral curvature of the spine combined with vertebral rotation that occurs in patients of 10. years of age or older until bone maturity (18-20. years of age). AIS is predominant in females. If untreated, the curvature could evolve with negative long-term prognosis including psychosocial impact, back pain, pulmonary compromise, cor pulmonale, and even death due to respiratory failure. Causes of the disease have been postulated to involve genetics, abnormal muscle, connective tissue and bone structures, and neuroendocrine disorders. Psychological pathways have also been studied. Little data, however, have been collected on bone turnover in these patients. Some studies demonstrated decreased bone mineral density which may be suggestive of increased osteoblast activity. Other studies suggested a correlation to abnormal platelet morphology. Alterations in the spinal muscle contractile function may be responsible for spinal curvature. Measurement of trace elements in serum revealed impaired zinc and selenium metabolism, probably secondary to hormonal deregulation. Subsequent endocrine studies suggested a role for leptin and growth hormone in AIS. Recently, a neuroendocrine hypothesis has been proposed. This theory involves a unique melatonin-signaling dysfunction and opens new frontiers in the elucidation of the pathologic mechanisms for onset and progression of this disease.