Background and aim: Perforation of the colon as a result of endoscopic manipulation is considered a severe adverse event. The goal of this review is to present the expected incidence of perforation in relation to varying levels of difficulty in endoscopic exploration and polypectomy together with the whole context of mechanisms, predisposing factors, diagnosis, and the strategic management plan. Methods: An extensive search was undertaken in the Medline database for recent articles (published from 2000 onwards) in the English language using specific terms relating to the reported frequency of perforation during diagnostic and therapeutic colonoscopy in various medical settings and including morbidity, mortality, and appropriate management. Additional articles were retrieved irrespective of publication date to supplement where necessary data on important issues such as mechanisms of perforation, risk factors, diagnosis, and prevention. Results: The frequency of perforation was found to be 1 in 1400 for overall colonoscopies and 1 in 1000 for therapeutic colonoscopies. Varying perforation rates have been estimated for polypectomies, endoscopic mucosal resections, and endoscopic submucosal dissections. The mortality has dropped to 0 % in most studies, with the highest reported percentage being 0.02 %. Advanced age, female sex, the presence of multiple co-morbidities, diverticulosis, and bowel obstruction have been shown to increase the risk of perforation. The decision between surgery and nonoperative treatment will depend on the type of injury, the quality of bowel preparation, the underlying colonic pathology, and the clinical stability of the patient. Conclusion: The perforation rate has declined in recent years in relation to more historical series, but there is now an increasing trend as a consequence of advanced interventional endoscopy. Awareness and experience are the only preventive measures that can limit the incidence of perforation.