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Awareness and practice of appropriate treatment for childhood sickle cell disease (SCD) has improved, and survival rates have increased significantly. Today, most patients will eventually require treatment in the adult-care setting. Adolescents who are transferred out from successful pediatric programs face numerous challenges regarding continuity of care, and mortality rates remain high in this age group. Here, we describe a systematic literature review conducted to examine the barriers to and approaches for successful transition of patients with SCD from adolescent to adult care. Articles were primarily located through the US National Library of Medicine (Pubmed.gov) and were omitted if their principal focus was not SCD transition treatment. A secondary search of 5 additional sources was conducted regarding relevant guidelines or meta-analyses. Current publications describe barriers to continuity of care in this group, proposals for improving the transition process, and contemporary models for SCD care transition. Clinical recommendations include development of a flexible, patient-centric transition plan and education for health care providers.