Purpose Ideal treatment timing in orthodontics is controversially discussed depending on the type and extent of the dysgnathia and malocclusion present, especially with regard to efficiency, patient burden and treatment efforts of early compared to regular or late treatment. This German clinical practice guideline aims to clarify, at which time points an orthodontic anomaly can be effectively treated and how treatment efficiency differs depending on treatment timing. Methods A systematic literature search was performed in various guideline databases and databases PROSPERO, MEDLINE (PubMed), Cochrane Library, Web of Science, ClinicalTrials.gov and the International Clinical Trials Registry Platform according to a predefined PICO (Population, Intervention, Comparison and Outcomes with added qualitative search terms) search algorithm and strategy. Appraisal of scientific evidence of the individual studies checked for eligibility was carried out according to SIGN (Scottish Intercollegiate Guidelines Network), AMSTAR II (Assessing the Methodological Quality of Systemic Reviews), and AXIS (Appraisal Tool to Assess the Quality of Cross-sectional Studies) tools. Only controlled studies with a high, acceptable or moderate quality (and thus an acceptable risk of bias) were considered. Results A total of 309 studies of over 11,000 sources screened were identified to be eligible for inclusion and critically appraised for study quality and risk-of-bias. No relevant guidelines relating to the aims of the present guideline were found. Elected delegates of in total 21 German scientific societies and organizations agreed upon a total of 19 evidence-based statements and recommendations based on a nominal consensus process. Conclusions Although most malocclusions can be effectively treated both in the early, late mixed, and permanent dentition, evidence suggests that therapy of a pronounced skeletal or dental class II anomaly can be started early to reduce the risk of dental anterior tooth trauma, whereas in a moderate class II anomaly, therapy can preferably be carried out before or during the pubertal growth peak. Therapy of a skeletal or dental class III anomaly should be started early, as this also reduces the need for later surgery to correct the anomaly. The treatment of a pronounced skeletal or dental transverse anomaly should be started early in the upper jaw in order to utilize the high adaptivity of the maxillary structures in young patients.