Introduction Adolescent idiopathic scoliosis (AIS) affects 1–3% of the population, but its pathogenesis remains unclear. The coexistence of musculoskeletal hypermobility and scoliosis in many inherited syndromes raises the possibility that isolated musculoskeletal hypermobility may contribute to AIS development or progression. Methods We performed a systematic review of the evidence for a relationship between isolated musculoskeletal hypermobility and AIS. A meta-analysis was planned, but if not possible, a narrative evidence synthesis was planned. Results Nineteen studies met eligibility criteria for inclusion. One study was excluded due to insufficient quality. Substantial heterogeneity in study design and methodology negated meta-analysis, so a narrative review was performed. Of the 18 studies included, seven suggested a positive association and eight found no association. Three reported the prevalence of musculoskeletal hypermobility in individuals with AIS. Overall, there was no convincing population-based evidence for an association between musculoskeletal hypermobility and AIS, with only two case–control studies by the same authors presenting compelling evidence for an association. Although populations at extremes of hypermobility had a high prevalence of spinal curvature, these studies were at high risk of confounding. Wide variation in methods of measuring musculoskeletal hypermobility and the challenge of assessing AIS in population-based studies hinder study comparison. Conclusions There is a paucity of high-quality evidence examining the association between isolated musculoskeletal hypermobility and AIS. Large-scale prospective studies with adequate adjustment for potential confounding factors could clarify the relationship between musculoskeletal hypermobility and AIS to elucidate its role in the pathogenesis of AIS.