The Global Collaboration for Resilient Food Systems (CRFS) is a program of the McKnight Foundation that has funded agricultural research since the 1980s. Currently, most grants support regionally based research projects that are grouped into three regional communities of practice (CoPs) in Africa and South America. A small portfolio of grants are cross-cutting in nature. Regional projects typically link international, national, and local organizations with communities of smallholder farmers, researchers, development professionals, and other stakeholders. Cross-cutting projects support aspects of work across regions or help to facilitate global-to-local connections. CRFS projects generate technical and social innovations to improve nutrition, livelihoods, productivity, environmental sustainability, rural vibrancy, and equity for farming communities. Large-scale impact is realized when new ideas, technologies, or processes are adapted to new contexts, when insights from research catalyze change in policy and practice, and when innovation inspires further success.