Actinomycosis has increasingly been recognized as a cause of persistent or recurrent periapical disease associated with endodontically treated teeth. This case report shows the classic clinical picture of periapical actinomycosis: persistent periapical disease with recurrent sinus tracts. Although there was no pain or swelling after clinically acceptable initial endodontic treatment, a periapical lesion developed. After retreatment, the periapical lesion persisted, and a sinus tract developed. The sinus tract healed with antibiotic therapy but recurred within a few months. This cycle of sinus tract to antibiotic therapy to recurrence of the sinus tract repeated several times over a period of 5 years. Upon biopsy, periapical actinomycosis was diagnosed, where classic "sulfur granules" were demonstrated in the histologic examination of the periapical lesion. Antibiotic therapy for a period of 6 weeks was prescribed subsequent to the histologic diagnosis because of the possibility of spread of the actinomycotic infection into the maxillary sinus. Considerable healing was evident within 5 months of surgical and antibiotic treatment. Keywords: antibiotic therapy, endodontic retreatment, endodontic treatment, periapical actinomycosis, periapical healing, periapical surgery