Numerous compounds exist in nature that can scavenge free radicals and thus have the potential to act as antioxidants in foods. Interest in natural free radical scavengers has resulted in tens of thousands of publications on various molecules and extracts but only an extremely small number have actually been used in commercial applications. The gap between research interest and commercial application is mainly due to the lack of bench top methods that can predict the efficacy of antioxidants in complex food matrices. This disconnection seems to be due to the extremely complex nature of lipid oxidation and antioxidant activity in even relatively simple food systems such as oil-in-water emulsions. This review highlights a number of areas where lack of knowledge is currently holding back our ability to predict which free radical scavengers will be good antioxidants in emulsions: non-free radical scavenging reactions of antioxidants; the existence of different types of oil-water interfaces; difficulties in characterizing lipid droplet surfaces; and differences in oxidation kinetics in different lipid droplets. Further research is needed to identify the key factors that determine antioxidant efficacy in complex heterogeneous systems. This knowledge would then increase our ability to predict how antioxidant structure and properties relate to their activity in food emulsions.