Scoliosis is diagnosed as idiopathic in 70 % of structural deformities affecting the spine in children and adolescents, probably reflecting our current misunderstanding of this disease. By definition, a structural scoliosis should be the result of some primary disorder. The goal of this article is to give a comprehensive overview of the currently proposed etiological concepts in idiopathic scoliosis regarding genetics, molecular biology, biomechanics, and neurology, with particular emphasis on adolescent idiopathic scoliosis (AIS). Despite the fact that numerous potential etiologies for idiopathic scoliosis have been formulated, the primary etiology of AIS remains unknown. Beyond etiology, identification of prognostic factors of AIS progression would probably be more relevant in our daily practice, with the hope of reducing repetitive exposure to radiation, unnecessary brace treatments, psychological implications, and costs-of-care related to follow-up in low-risk patients.