Burkitt lymphoma (BL) is the most common pediatric cancer in sub-Saharan Africa (SSA), and also occurs frequently among adolescents and young adults (AYAs), often associated with HIV. Treating BL in SSA poses particular challenges. Although highly effective, high-intensity cytotoxic treatments used in resource-rich settings are usually not feasible, and lower-intensity continuous infusion approaches are impractical. In this article, based on evidence from the region, we review management strategies for SSA focused on diagnosis and use of prephase and definitive treatment. Additionally, potentially better approaches for risk stratification and individualized therapy are elaborated. Compared with historical very low-intensity approaches, the relative safety, feasibility, and outcomes of regimens incorporating anthracyclines and/or high-dose systemic methotrexate for this population are discussed, along with requirements to administer such regimens safely. Finally, research priorities for BL in SSA are outlined including novel therapies, to reduce the unacceptable gap in outcomes for patients in SSA vs high-income countries (HICs). Sustained commitment to incremental advances and innovation, as in cooperative pediatric oncology groups in HICs, is required to transform care and outcomes for BL in SSA through international collaboration.