This study explores the psychosocial problems experienced by families with children aged 6 to 14 years suffering from beta-thalassemia major (N = 188). The psychosocial problems and the family's adjustment to the effects of the illness were compared across a number of cultures where the disease is prevalent, namely Cyprus, Greece, and Italy. A small number of migrant children in the United Kingdom was also included in the study. Semi-structured interviews were conducted with parents who also completed the Rutter Parental Questionnaire and the Goldberg General Health Questionnaire. Teachers were asked to complete a Children's Behaviour Questionnaire designed by Rutter. In all countries the disease seemed to have a binding effect on the family, thus mobilizing adaptive mechanisms. Father's low education level and the presence of major medical complications were predictors of poor family adjustment. Differences between and within countries may well reflect differences in health policies, existing level of socio-economic development, and in the cultural patterns in coping with a chronic illness.