The autonomic nervous system through its hypothalamic neuroendocrine control of puberty, skeletal growth and menarche contributes importantly to the pathogenesis of adolescent idiopathic scoliosis (AIS). Melatonin dysfunction detected in AIS subjects also involves the autonomic nervous system. The thoracospinal concept for the pathogenesis of right thoracic AIS in girls thought by some to result from dysfunction of the sympathetic nervous system (SNS), is supported by recent vascular and peripheral nerve studies. Lower body mass index (BMI).in girls with AIS is associated with decreased circulating leptin levels. Leptin, secreted by adipocytes, is a master hormone with many regulatory functions for growth and reproduction, including: 1) appetite repression, anorexigenic; 2) initiation of puberty in girls in a permissive action, and 3) in mice, longitudinal bone growth, chondrogenic and angiogenic, and in bone formation, antiosteogenic acting centrally through the SNS and possibly directly. In AIS girls, autonomic nervous system activity was reported to be higher than in controls. We suggest that in AIS susceptible girls, given adequate nutrition and energy stores, circulating leptin talks to the hypothalamus where dysfunction leads to an altered sensitivity to leptin resulting in increased SNS activity contributing with neuroendocrine mechanisms to: 1) earlier age at, and increased peak height velocity, 2) general skeletal overgrowth, 3) earlier skeletal maturation, 4) extra-spinal skeletal length asymmetries, including periapical ribs and ilia, 5) generalized osteopenia, and 6) lower BMI. The SNS-driven effects may also add adventitious changes to the spine including asymmetries complicating the neuroendocrine effects on adolescent spinal growth. In AIS pathogenesis, the leptin-SNS concept is complementary to our NOTOM escalator concept involving the somatic nervous system. Together these two concepts view AIS in girls as being initiated by a hypothalamic dysfunction of energy metabolism (bioenergetics) affecting skeletal growth in the trunk. Where, in susceptible girls, the postural mechanisms of the somatic nervous system fail to control the asymmetric spinal and/or rib growth changes in a rapidly enlarging adolescent spine; this failure becomes evident as mild back-shape shape asymmetry, or scoliosis. The environmentally-enhanced stature of normal subjects in the last 300 years, in girls susceptible to AIS, may have exaggerated any developmental dysharmony between the autonomic and somatic nervous systems being fought out in the spine and trunk of the girl – possibly making mild back-shape asymmetry, or scoliosis more prevalent today than hitherto.