This paper focuses on the psychological and social factors that influence the adjustment process of children and adolescents with chronic conditions, primarily sickle cell disease. A review of the literature will reveal that psychological variable, such as anxiety and depression affecting adjustment, are the most studied. However, it will be pointed out that social variables such as family, school, and peers, also play a major role in this process. Furthermore, in keeping with the approach of this special collection, these psychological issues will be discussed within a developmental context. Clinical teams and practitioners are encouraged to take a longitudinal-biopsychosocial approach in addressing the needs of these children and their families. By doing so, they will be able to meet the present and long term psychological, social, educational, as well as medical needs of children and adolescents with sickle cell disease and other chronic conditions, and their families. This approach will also allow professionals to recognize and utilize the strengths of this population in the promotion of their overall well-being.