Apical periodontitis is an inflammation of dental periapical tissues developed as a response to colonization of microorganisms in root canal system. Etiology of periapical pathology is associated with different species of microorganisms that are not fully defined yet. The changes in the composition of root canal microbiota as well as other factors, such as host resistance to various infections and concomitant viral infection, etc., can influence development of the symptomatic apical periodontitis. Etiology of disease is reviewed in this article. The purpose of treatment of symptomatic apical periodontitis is to eliminate the infection in root canal system and to obtain relief of symptoms. It can be done by conventional root canal therapy, which can be combined with anti-inflammatory medication. Indications for antibiotic therapy in such cases are limited to particular occasions, which are considered in article. Nevertheless, findings show that usually dentists prescribe antibiotics improperly in clinical practice. It can render drugs ineffective against diseases of dental origin as well as against potentially fatal infectious diseases. Selection of antibiotics for the treatment of root canal infections is reviewed in this article. Importance of antimicrobial susceptibility testing is emphasized. There is a need for more research on microbial causes and interactions in different forms of apical periodontitis to improve diagnosis and treatment.