Prompted by the growth of managed care and the American Psychological Association's recent guidelines for treatment efficacy studies, we have struggled with the challenges associated with devising and implementing manualized family intervention programs for pediatric patients. This manuscript outlines the strengths and challenges of controlled manual-based family interventions for medically ill children, using pediatric sickle cell disease (SCD) as an example. A culturally and developmentally sensitive intervention program, designed for the researcher's subject population (African American, low SES, inner city) is discussed. Possible solutions to the challenges of conducting family-oriented intervention efficacy studies with pediatric populations are presented.