Most children and adolescents with sickle cell disease are managed by primary care physicians. Sickle cell disease is often considered to be a disorder that is only associated with treatment of acute pain, although it has become evident over the years that the condition is associated with numerous organ complications, many of which begin during adolescence. The purpose of this article is to highlight the various organ complications that may occur in sickle cell disease, with a particular emphasis on adolescence, and how best to detect and screen for such complications. Furthermore, as life expectancy continues to improve, transition to adult health care for patients has become a critical issue. The psychological effect on the adolescent with this chronic illness, as well as a brief description of the transitional processes to adult-centered care, are discussed.