Nepal has a rich history of vitamin A research and a national, biannual preschool vitamin A supplementation (VAS) programme that has sustained high coverage for 25 years despite many challenges, including conflict. Key elements of programme success have included (a) evidence of a 26–30% reduction in child mortality from two, in-country randomized trials; (b) strong political and donor support; (c) positioning local female community health volunteers as key operatives; (d) nationwide community mobilization and demand creation for the programme; and (e) gradual expansion of the programme over a period of several years, conducting and integrating delivery research, and monitoring to allow new approaches to be tested and adapted to available resources. The VAS network has served as a platform for delivering other services, including anthelmintic treatment and screening for acute malnutrition. We estimate that VAS has saved over 45,000 young lives over the past 15 years of attained national coverage. Consumption of vitamin A- and carotenoid-rich foods by children and women nationally remains low, indicating that supplementation is still needed. Current challenges and opportunities to improving vitamin A status include lower VAS coverage among younger children (infants 6–11 months of age), finding ways to increase availability and access to dietary vitamin A sources, and ensuring local programme investments given the recent decentralization of the government.