In the last two decades, remarkable progress in the treatment of children with acute lymphoblastic leukemia has been achieved in many low- and middle-income countries (LMIC), but survival rates remain significantly lower than those in high-income countries. Inadequate supportive care and consequent excess mortality from toxicity are important causes of treatment failure for children with acute lymphoblastic leukemia in LMIC. This article summarizes practical supportive care recommendations for healthcare providers practicing in LMIC, starting with core approaches in oncology nursing care, management of tumor lysis syndrome and mediastinal masses, nutritional support, use of blood products for anemia and thrombocytopenia, and palliative care. Prevention and treatment of infectious diseases are described in a parallel paper.