The primary objective of endodontic therapy is to create a biologically acceptable environment within the root canal system that allows for the healing and maintenance of the health of the peri-radicular tissue. Bacteria are one of the main causes of pulp problems, and they have different methods of penetrating and invading the endodontic space such as through carious lesions, traumatic pulp exposures, and fractures. The types of bacteria found range from facultative anaerobes to aerobes, up to the most resistant species able to survive in nutrient-free environments; the bacterial species Enterococcus faecalis belongs to this last group. Enterococcus faecalis is considered one of the main causes of recurring apical periodontal lesions following endodontic treatment, with persistent lesions occurring even after re-treatment. The review presented in this paper was performed in accordance with the PRISMA protocol and covers articles from the related scientific literature that were sourced from PubMed, Scopus, and Google Scholar using the following terms as keywords: “endodontic treatment”, “endodontic bacteria”, “microbial endodontic”, and “endodontic failure”. Only the articles considered most relevant for the purposes of this paper were read in full and taken into consideration for the following review. The results show that Enterococcus faecalis, Actinomycetes, and Propionibacterium propionicum are the species most frequently involved in persistent radicular and extra-radicular infections.