This research article examines HarvestPlus’ efforts (2003 to 2016) to improve nutrition through biofortification, and contains key lessons pertaining to the production, marketing, and delivery of biofortified crops globally. The authors find that about 20 million people in 4 million households now grow and consume biofortified crops in eight HarvestPlus target countries– Bangladesh, DR Congo, India, Nigeria, Pakistan, Rwanda, Uganda, and Zambia. These crops include vitamin-A orange sweet potato (OSP), iron beans, and zinc rice, which have been shown to increase body stores of micronutrients and to combat conditions like vision loss and cognitive deficiencies. In spite of the widespread successes attributable to biofortification, scaling remains a challenge in three primary areas: 1) mainstreaming into public plant breeding programs; 2) building consumer demand; and 3) integrating into public and private policies, programs, and investments. The authors conclude that institutional leadership is needed to continue to drive towards this ambitious goal.