Global pediatric surgery exists to address the great disparity in disease burden between the world’s richest and poorest children. As the landscape has rapidly evolved and includes isolated clinical humanitarian trips, long-term medical missions, academic partnerships, and other models, it is essential to evaluate the ethical framework governing the methods of engagement. Partners from low- and middle-income countries (LMICs) and high-income countries (HIC) must maintain open communication and proper accountability. Clinical programs must above all seek the best outcome for the patient in a culturally appropriate manner with mutual respect. Surgical education programs must be developed to empower LMIC surgeons, and research agendas should be developed according to the needs identified by LMIC surgeons and patients. In this chapter, specific challenges are presented with practical suggestions for humble engagement that utilize the strengths of both LMIC and HIC surgeons.