In the contemporary era of "patient-centered medicine", our evidence-based effort is focused on the identification of individual factors of responsiveness to therapy; and orthodontics is no exception. This lecture will illustrate the biological and morphological characteristics of the patient that can make a difference in the outcomes of treatment of Class II malocclusion. The results of a series of clinical trials performed in the last 10 years assist in the definition of ideal candidates to alternative treatment strategies for Class II patients.