Bacteria are the primary causative agents in the development and progression of pulpal and periapical diseases. The main objective of endodontic treatment is to eliminate as many microorganisms as possible from the root canal system and to create conditions that prevent the survival and proliferation of any remaining bacteria. This goal can be achieved through a combination of local and systemic antimicrobial therapy. During endodontic treatment, antibiotics may be administered systemically or locally to help establish and maintain an aseptic environment. This review discusses the role, indications, and applications of antibiotics in endodontic practice.