Background: Colonoscopy is the gold standard for adenoma detection. All endoscopists who perform colonoscopy must by mandate be skilled to perform polypectomy. However, there are significant differences between endoscopists in terms of the polyp detection rate and in the effectiveness of polypectomy. Summary: Most polyps identified can be managed by conventional polypectomy and do not pose a significant challenge for resection to an adequately skilled and trained endoscopist. Up to 15% of polyps may be considered “difficult”, unsuitable for conventional endoscopic removal because of size, morphology, site, or access grade. Endoscopist-, patient- and polyp-specific viewpoints influence the management of difficult polyps. Advances in endoscopic resection techniques have led to extended indications for polypectomy. Conventional endoscopic removal of colorectal polyps is associated with a small but not negligible incidence of complications, most commonly bleeding and perforation. Advanced techniques for difficult polyps can potentially cause significant, even life-threatening complications. In addition, in the presence of “difficult” polyps, complications are more common. Key Messages: Multiple techniques are now available for the resection of difficult polyps. The endoscopist should individualize the appropriate approach for the treatment of difficult polyp in order to maximize oncological safety, efficacy and minimize complications and unnecessary surgery.