The major role of colonoscopy with polypectomy in reducing the incidence of and mortality from colorectal cancer has been firmly established. Yet there is cause to be uneasy. One of the most striking recent findings is that there is an alarmingly high incomplete polyp removal rate. This phenomenon, together with missed polyps during screening colonoscopy, is thought to be responsible for the majority of interval cancers. Knowledge of serrated polyps needs to broaden as well, since they are quite often missed or incompletely removed. Removal of small and diminutive polyps is almost devoid of complications. Cold snare polypectomy seems to be the best approach for these lesions, with biopsy forcep removal reserved only for the tiniest of polyps. Hot snare or hot biopsy forcep removal of these lesions is no longer recommended. Endoscopic mucosal resection and endoscopic submucosal dissection have proven to be effective in the removal of large colorectal lesions, avoiding surgery in the majority of patients, with acceptably low complication rates. Variants of these approaches, as well as new hybrid techniques, are being currently tested. In this paper, we review the current status of the different approaches in removing polypoid and nonpolypoid lesions of the colon, their complications, and future directions in the prevention of colorectal cancer.