One of the most debated and controversial topics in orthodontics is the role of early treatment in the management of Class II malocclusions. Dento-skeletal Class II malocclusions associated with mandibular retrognathism are highly prevalent in growing patients and frequently raise a critical clinical question: whether treatment should be initiated during growth or postponed until the permanent dentition. Several clinical considerations support early intervention, including the elimination of deleterious oral habits, reduction of the risk of incisal trauma, improvement of facial aesthetics, and positive effects on a child’s self-esteem achieved through a more harmonious smile at an early age. Nevertheless, the orthodontic literature is not unanimous regarding the true skeletal benefits of early treatment, particularly with respect to mandibular growth stimulation using functional appliances. Current evidence indicates that such treatment should only be considered after a careful and accurate differential diagnosis. A correct differential diagnostic approach is essential to distinguish between dentoalveolar components and different skeletal types of mandibular retrusion, to assess individual growth potential, and to identify patients who may truly benefit from functional orthopedic treatment. Without this individualized evaluation, early intervention may result in changes that are predominantly dental, temporary, or unstable over time. This lecture emphasizes the fundamental role of differential diagnosis in the early management of dento-skeletal Class II malocclusions and outlines relevant criteria for selecting appropriate candidates for functional treatment. Particular attention is devoted to the long-term stability of treatment outcomes. Scientific evidence is presented through the analysis of patients treated with the Frankel Functional Regulator (FR-2), with a follow-up period extending beyond 20 years, demonstrating that stable skeletal and occlusal changes can be achieved when treatment is correctly indicated and appropriately timed. These findings underline a key clinical message: early treatment of Class II malocclusions associated with mandibular retrusion can lead to lasting results, but only when based on sound diagnosis, appropriate appliance selection, and realistic therapeutic objectives.