This thesis focuses on the general regulation of novel bacteria, particularly probiotics that are intended for human consumption. Within the European Union, the regulation of novel bacteria remains challenging and expensive for applicants. The European regulatory framework contains grey zones in regards to genetically modified microorganism, substantial equivalence of related bacterial strains, and application of the European Qualified Presumption of Safety (QPS) system. Examples of these grey zones are discussed within this work. The first discussed example is Lactobacillus reuteri, strain DSM 17938, and the regulation surrounding it as a genetically modified microorganism and conventional probiotic. Antibiotic resistance plasmids were removed from the mother strain (ATCC 55730) by techniques that are not considered as genetic modification by consulted experts and European law. It is likely that the mother and the daughter strains are substantially equivalent and therefore safe. Another example of a novel bacteria is the commensal and abundant bacterium Akkermansia muciniphila. According to current scientific findings, this recently detected mucus degrader shows great potential at reducing health costs through disease prevention. The bacterium has not gained QPS or “novel food” status in terms of the Novel food Regulation (EC) No 258/97, but seems to be safe for future commercial production. Therefore, scientific work should focus on the functionality and importance of Akkermansia spp. in humans to facilitate the launch of novel probiotic formulations. Based on these examples, we can see that the repertoire and possibilities of proposed new probiotic candidates has not been exhausted.