Apical periodontitis has a microbial aetiology and is one of the most common inflammatory diseases that affect humans. Fungi, archaea and viruses have been found in association with apical periodontitis, but bacteria are by far the most prevalent and dominant microorganisms in endodontic infections. Bacterial infection of the root canal system only occurs when the pulp is necrotic or was removed for previous treatment. In some specific cases, including acute and chronic abscesses, the bacterial infection may reach the periradicular tissues. Intracanal bacteria are usually observed as sessile multispecies communities (biofilms) attached to the dentinal root canal walls. Infection in the main root canal lumen can spread to other areas of the root canal system. Although more than 500 bacterial species have been detected in endodontic infections, a selected group of 20 to 30 species are most frequently detected and may be considered as the core microbiome. There is a high interindividual variability in the endodontic microbiome in terms of species composition and relative abundance. Obligate anaerobic species are more abundant in the intraradicular bacterial communities of teeth with primary apical periodontitis, while both anaerobes and facultatives dominate the communities in post-treatment apical periodontitis. Bacterial interactions play an essential role in determining the overall virulence of the community, which has been regarded as the unit of pathogenicity of apical periodontitis. This article reviews the microbiologic aspects of endodontic infections and provides perspectives for future research and directions in the field.