"Flare-ups" during or following endodontic treatment are not uncommon. A "Flare-up" refers to post-operative pain and/or swelling resulting from bacterial, mechanical or chemical irritation. Prompt diagnosis and treatment are essential for reducing patients' pain and discomfort. Prevention of bacterial, chemical or mechanical invasion to the periapical tissues is the best approach. Other treatment modalities which reduce the probability of periradicular tissue irritation should also be adopted. Etiology, prevention, diagnosis and treatment options of "flare-up" cases are discussed as well as indications for analgesics, in accordance with the severity of the pain.