Neonatal screening for hemoglobinopathies, coupled with comprehensive medical care that includes parental education, prophylactic penicillin, and immunizations, has markedly reduced mortality from sickle hemoglobinopathies during infancy and early childhood. However, despite an increased knowledge of pathophysiology, current therapy does little to prevent acute, noninfectious complications such as anemic crises, pain events, or strokes; nor does it reliably prevent or delay the development of chronic organ damage. Recent publications have increased our understanding of factors that contribute to the clinical heterogeneity of sickle hemoglobinopathies, improved modestly our ability to identify and treat acute complications, and provided real hope for the development of potentially curative therapies. Prospective therapeutic trials of hydroxyurea and of bone marrow transplantation have recently begun.