Sickle cell disease (SCD) occurs in 1 of every 400 to 500 African American births. Despite its prevalence, there has been a relative dearth of attention paid to SCD in the psychological literature. African American SCD adolescents and young adults, individuals at an already vulnerable developmental stage, are at increased risk for psychological distress and psychosocial impairments (e.g., depression and low self-esteem, poor social and academic/vocational functioning). Such difficulties often result in problematic adherence to medical regimens, and thus represent a potentially serious clinical and public health problem that merits the attention of psychologists working in medical settings. This article (1) reviews the psychosocial needs peculiar to SCD patients transitioning from adolescence to young adulthood; (2) applies a culturally informed stress-coping-adjustment framework to assess and address the psychological status, psychosocial functioning, and disease outcomes of these individuals; and (3) describes a culturally and developmentally sensitive, psychoeducational group intervention.