Bacteria are the prime cause of periapical diseases and root canal microbiology is a well‐researched area of endodontics. Antigen‐presenting cells (APCs) are present in periapical lesions of endodontic origin and play a substantial role in recognizing, processing and presenting pathogenic antigens to the adaptive immune system such as an effective and long‐lasting immune response is generated against the specific pathogens. Toll‐like receptors (TLRs) are germ‐line encoded pathogen recognition receptors (PRR) expressed by various APCs which induce their maturation, lead to gene transcription in the nucleus and the production of several pro‐ and anti‐inflammatory cytokines. Thirteen TLRs have been discovered, 10 of which have been identified in humans so far. Preliminary studies of dental pulp tissue have demonstrated various cell types expressing different TLRs in response to commonly encountered microorganisms. However, there is little information available regarding the expression and function of the various TLRs in human periapical lesions. This review discusses the interactions of various APCs in periapical lesions and the possible roles of different TLRs and APCs in pulp/periapical pathogen recognition and presentation to the adaptive immune system in the initiation and sustaining of periapical diseases.