Long-term medication adherence in resource-limited settings often presents significant challenges, yet sustained therapeutic benefits can transform disease outcomes for conditions requiring lifelong management. A decade-long follow-up of Ugandan children with sickle cell anemia receiving hydroxyurea demonstrates the feasibility and sustained clinical benefits of this fetal hemoglobin-inducing therapy in sub-Saharan Africa, where sickle cell disease affects millions but treatment access remains limited. The extended treatment period showed consistent reductions in painful vaso-occlusive crises, hospitalizations, and mortality rates compared to historical controls. Patients maintained elevated fetal hemoglobin levels throughout the study period, with the medication's protective effects persisting even as children transitioned through adolescence into young adulthood. This represents one of the longest prospective studies of hydroxyurea in an African population, where genetic modifiers and environmental factors may influence treatment response differently than in previously studied populations. The findings provide crucial evidence for healthcare policy makers considering hydroxyurea implementation in resource-constrained settings. While the medication requires regular monitoring for potential bone marrow suppression, the study suggests that simplified monitoring protocols can maintain safety while improving accessibility. The research addresses a critical gap in sickle cell management globally, as approximately 75% of annual sickle cell births occur in sub-Saharan Africa. The sustained benefits observed challenge assumptions about medication compliance in low-resource settings and support expanded access to this life-changing therapy. However, questions remain about optimal dosing strategies for different genetic backgrounds and the long-term effects on fertility and organ function that warrant continued surveillance.