Foodborne disease is a major global health challenge, causing millions of illnesses every year – mostly in low- and middle-income countries – and hindering achievement of other global goals, such as improved nutrition. Since contamination of food can happen at any point ‘from farm to fork’, reducing the burden of foodborne illness requires a whole-of-food-system approach: one that considers all actors and activities that play a role in production, processing, distribution, preparation, and consumption of food. The objective of this paper is to discuss how to enact such a food system approach to food safety, with a focus on LMICs.