Flexible sigmoidoscopy (FS), colonoscopy, and colonoscopic polypectomy have revolutionized the science and practice of gastroenterology. The scientific understanding of many gastrointestinal diseases, including colon cancer, has been greatly advanced by serial colonoscopy with colonoscopic biopsy. Millions of colonoscopies are performed annually in the United States for indications such as colon cancer screening or surveillance, gastrointestinal bleeding, or other gastrointestinal conditions, and for therapies such as colonoscopic polypectomy, hemostasis, or colonic decompression. General internists, as well as other nongastroenterologists, must become familiar with the indications, contraindications, techniques, sensitivity, limitations, and risks of these ubiquitous procedures. This article comprehensively reviews the techniques, indications, and contraindications of FS and colonoscopy, with a focus on diagnostic endoscopy.