Purpose <p>The objective of this systematic review was to identify and evaluate the quality of the available evidence on the orthodontic aspects and implications when treating patients with MIH, before, during and after orthodontic treatment.</p> Methods <p>Six electronic bibliographic databases were searched up to 26.05.2026. All studies assessing orthodontic interventions and outcomes in 5–18-year old patients with MIH were considered as eligible for inclusion. Qualitative and quantitative synthesis of results were performed and reported according to the PRISMA guidelines.</p> Results <p>Out of 243 records identified, 5 studies were included: a prospective, split-mouth trial, a prospective cohort, a cross-sectional study, and 2 retrospective studies. The included studies evaluated the relationship between MIH, extraction timing, space closure outcomes, adjacent teeth eruption and angulation, and orthodontic outcomes in paediatric populations. The relationship between MIH and orthodontic treatment was primarily therapeutic, rather than aetiological. Maxillary extractions yielded more favourable spontaneous space closure compared to mandibular extractions. This was confirmed after pooling the estimates for complete space closure after first molar extraction of 3 studies (no orthodontic treatment need versus orthodontic treatment need) in the maxilla: RR 4.12, 95% CIs: 1.44,11.80 and no orthodontic treatment need versus orthodontic treatment need in the mandible: RR 1.36, 95% CIs: 0.63, 2.91.</p> Conclusion <p>Management of severely affected first permanent molars through extraction creates orthodontic considerations that should be addressed through appropriate timing, patient selection, and interdisciplinary collaboration. The literature presents notable gaps; no reliable data on the optimal timing to extract severely affected FPMs could be identified.</p>