This article focused on two hematologic diseases that have received significant attention in the pediatric literature: sickle cell anemia and hemophilia. As the data indicate, these illnesses present lifelong challenges to individuals afflicted. With advances in medical interventions, many children with these hematologic diseases are living longer and with fewer serious complications. Intervention efforts only recently have begun to consider issues related to quality of life and increased psychological adjustment, including active coping strategies by children and their parents and necessary social support for all family members. Theoretical models [54] have highlighted the multiple factors that play a role in illness adjustment and the complex interactions of these factors. Individual, family, and community characteristics are impacted by and, in turn, impact on illness-related characteristics. The notion that illness severity is predictive of psychological adjustment has been discarded in favor of a model that recognizes multiple influences and multiple outcomes. Child coping, parent coping, social support, adaptive functioning, treatment compliance, and illness severity are being considered to better understand and influence overall psychological functioning. The field of pediatric psychology has made tremendous advances in improving knowledge of illness and its impact on development. Even with these advances, however, there remains much to be discovered. To date, pediatric psychology research has focused primarily on individual illness categories, making comparisons across illness types difficult. By considering different illnesses within the same study, characteristics that are crucial to improved adjustment and common across illnesses can be identified. As we continue to work for cures for these debilitating illnesses, our goal remains to improve quality of life for children.