Recently the presence of fatty acid esters of 3-mono-chloro-1,2-propanediol (3-MCPD esters) has been reported in various types of foods and food ingredients, especially in refined vegetable oils. Although no evidence is available indicating any adverse effects, the safety significance of these substances in food is difficult to appreciate because of the lack of data. In addition, it is increasingly acknowledged that the safety of chloropropanol-esters in food cannot be established through the consideration of 3-MCPD esters in isolation. These chemicals are formed over processing together with other structurally related and toxicologically relevant molecules. Risk assessment has to consider all of them. This triggers significant analytical and toxicological challenges. Setting priorities, such as on precautionary mitigation, is likely to be necessary.