The increased longevity of patients with thalassemia and sickle cell disease (SCD) introduces new clinical challenges due to the accumulation of disease-related morbidity, psychosocial issues and health care adjustments. Patients with thalassemia major now live into adulthood without suffering heart failure but must confront delayed puberty, impaired fertility and progressive bone disease. The increased survival in SCD brings to the front previously unrecognized complications including pulmonary hypertension, silent cerebral infarcts and also reproductive dysfunction. Adolescents and young adults (AYAs) have age-related psychosocial needs in their transition from the pediatric health care environment to the adult system. In this review we present the uniquely age-related medical issues facing the AYA thalassemia and SCD cohort in their transition into adulthood.