Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for children with confirmed Sickle cell anemia (SCA) between 12 months and 10 years. Sickle cell anemia (SCA) is among the world’s most common forms of inherited hemolytic anemia, and results in significant morbidity and early mortality.  SCA is most prevalent in Africa, with as many as 300,000 babies born annually, representing up to 2% of newborns in some sub-Saharan countries. Assuming most of these babies die early in childhood, the World Health Organization (WHO) estimates that SCA causes 6-16% of under-five mortality for many African countries,  and this burden is projected to further increase substantially in the next 40 years. This alarmingly high contribution of SCA to under-five mortality makes the recognition and management of SCA an important cornerstone of efforts by many African countries toward achieving Millennium Development Goal #4, the reduction of child mortality.  Since deaths due to SCA mostly occur in children under 5 years old, efforts to save lives must include early diagnosis and treatment.  In addition to early death, SCA also causes profound adverse effects among surviving children on their education and future employment with resultant loss of productivity.  As the overall mortality declines in the region due to demographic transition, along with the expansion of vaccine and malaria control programs, the economic and health burden of non-communicable diseases such as SCA will undoubtedly increase proportionately and consume significant medical and social resources in Africa. WHO has recently recognized SCA as a significant health problem for Africa and recommends that sub-Saharan countries develop screening and treatment programs for SCA. With the development and implementation of newborn screening and treatment programs, the early mortality of SCA is likely to be significantly reduced; however, these interventions will not treat or cure the underlying disease.  Increased identification of SCA from public awareness and widespread screening efforts are likely to increase the perceived morbidity and burden of SCA in these countries, with many more children identified by screening, surviving early childhood, and suffering from its medical complications.  Accordingly, the introduction of hydroxyurea, as a once-daily inexpensive oral medication with a well-established short-term safety profile, is an intriguing and potentially ideal option for affected patients with SCA in the developing world, since access and safety of other potential therapeutic options, primarily transfusions or stem cell transplantation, are currently not realistic options.