Background: Micronutrient deficiencies affect over one quarter of the world’s population. Biofortification is an evidence-based nutrition strategy that addresses some of the most common and preventable global micronutrient gaps and can help improve the health of millions of people. Since 2013, HarvestPlus and a consortium of collaborators have made impressive progress in the enrichment of staple crops with essential micronutrients through conventional plant breeding. Objective: To review and highlight lessons learned from multiple large-scale delivery strategies used by HarvestPlus to scale up biofortification across different country and crop contexts. Results: India has strong public and private sector pearl millet breeding programs and a robust commercial seed sector. To scale-up pearl millet, HarvestPlus established partnerships with public and private seed companies, which facilitated the rapid commercialization of products and engagement of farmers in delivery activities. In Nigeria, HarvestPlus stimulated the initial acceptance and popularization of vitamin A cassava using a host of creative approaches, including “crowding in” delivery partners, innovative promotional programs, and development of intermediate raw material for industry and novel food products. In Uganda, orange sweet potato (OSP) is a traditional subsistence crop. Due to this, and the lack of formal seed systems and markets, HarvestPlus established a network of partnerships with community-based nongovernmental organizations and vine multipliers to popularize and scale-up delivery of OSP. Conclusions: Impact of biofortification ultimately depends on the development of sustainable markets for biofortified seeds and products. Results illustrate the need for context-specific, innovative solutions to promote widespread adoption.