Although childhood acute lymphoblastic leukemia (ALL) is curable, global disparities in treatment outcomes remain. To reduce these global disparities in low-middle income countries (LMIC), a paradigm shift is needed: start with curing low-risk ALL. Low-risk ALL, which accounts for >50% of patients, can be cured with low-toxicity therapies already defined by collaborative studies. We reviewed the components of these low-toxicity regimens in recent clinical trials for low-risk ALL and suggest how they can be adopted in LMIC. In treating childhood ALL, the key is risk stratification, which can be resource stratified. NCI standard-risk criteria (age 1-10 years, WBC < 50,000/uL) is simple yet highly effective. Other favorable features such as ETV6-RUNX1, hyperdiploidy, early peripheral blood and bone marrow responses, and simplified flow MRD at the end of induction can be added depending on resources. With limited supportive care in LMIC, more critical than relapse is treatment-related morbidity and mortality. Less intensive induction allows early marrow recovery, reducing the need for intensive supportive care. Other key elements in low-toxicity protocol designs include: induction steroid type; high-dose versus low-dose escalating methotrexate; judicious use of anthracyclines; and steroid pulses during maintenance. In summary, the first effective step in curing ALL in LMIC is to focus on curing low-risk ALL with less intensive therapy and less toxicity.