Microbial control agents (MCAs) are promising for use in sustainable agriculture. Nevertheless, they face a major hurdle in the registration process of the European Union, one reason being unclear data requirements on metabolites. This review examines the EU regulatory perspective on metabolites of MCAs for plant protection and identifies some key issues and concerns. Current data requirements for secondary metabolites of micro-organisms are based on degradation products/metabolites of chemicals. We conclude that this has contributed strongly to the current confusion regarding how to best evaluate potential production of toxic substances by MCAs. We suggest that data requirements should be revised and/or need guidance fit for purpose, in order to give the EU-regulation for MCAs a stronger base in microbiological knowledge. We also suggest implementation of a basic hazard assessment. If this is passed without any concerns, the production of unknown, potentially toxic, substances does not need to be further investigated.