The past 100 years since James Herrick's first description of sickle cell disease in the United States have been characterized by the gradual development of management strategies. We review the progress in sickle cell disease management in the United States over the past 100 years, with emphasis on the diverse forces surrounding advances in disease management. Mortality and survival data are presented chronologically, with an attempt to highlight improvements in survival associated with specific advancements for pediatric and adult care. Finally, the future course for sickle cell disease management is explored, given the continued work in advancing the field. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc.