Food loss and waste from the initial stages of food production to consumption is causing a growing concern. As yet, no food safety issues have been linked to food loss and waste, but numerous incidences of failure to comply with regulatory criteria have resulted in outbreaks of foodborne disease and food recalls due to microbiological or chemical hazards in the food. Overly extensive food safety concerns through exacting regulatory standards and quality control also cause enormous losses worldwide. In this chapter, we review the food safety challenges and drawbacks at each stage of the food supply chain by discussing relevant cases and their contribution to food loss and waste. The disparities between developing and developed countries are addressed to underline the global effect of food safety policies on food production and waste. Recent food safety trends and initiatives are also discussed.