The cognitive, biological, and psychological characteristics of adolescents affect their adaptation to a chronic medical condition. This article reviews the literature on how sickle cell disease alters the normal developmental challenges facing adolescents. Examples of these challenges include delayed maturation, neurologic complications, sequelae of pain episodes, and prolonged financial and family dependence. These challenges are also discussed within the context of family and peer relationships, as well as cultural norms. Using the principles of anticipatory guidance, interventions into the psychological development may help to preserve normal functioning. These interventions need to be provided in a manner acceptable to the adolescent within the community context. The education, counseling, and medical services provided by the multidisciplinary team in the Comprehensive Sickle Cell Program at Children's Hospital in Columbus, Ohio are used to highlight these intervention strategies.