Transitioning from pediatric to adult care is a challenging process for adolescents with sickle cell disease (SCD). There is a critical need for well-designed and practically adaptable SCD transition programs that are compatible within the social and cultural context of the individual. The purpose of this article is to outline the design of a theoretically informed intervention to facilitate successful transition for adolescents and young adults (AYAs) diagnosed with SCD. The authors propose and describe the use of a developmental–ecological framework in creating and implementing the Sickle Cell Disease–Age Based Curriculum for Transition (SCD-ABC). The SCD-ABC Transition program’s framework begins at birth with the parent–caregiver and spans throughout a child’s development into young adulthood. This program involves a multidisciplinary team approach with collaboration from pediatric and adult medical providers, family and peers, social services, the community, and adult mentors living with SCD. The goal of this program was to foster increased disease knowledge and self-efficacy for AYAs and ultimately facilitate successful transition to adult care. Finally, this review will present preliminary data from the SCD-ABC Transition program and discuss opportunities for broader applicability of this model to adolescents and young adults with SCD.