Colorectal cancer (CRC) remains the third most commonly diagnosed cancer and second leading cause of cancer death in the United States. Declines in CRC incidence and mortality over the past 20 years were attributed to CRC screening. Yet, only slightly more than half of the eligible at-risk population acknowledge being screened. To effectively meet the demands of screening in an enlarging, ethnically diverse, and aging population, a variety of modalities are needed. This article provides a focused assessment of effectiveness, limitations, and alternative available screening methods. New modalities endorsed in the updated guidelines (eg, fecal immunochemical tests, fecal DNA, and CT colonography) are reviewed. In addition, advances and updates in existing tests (eg, guaiac-based fecal occult blood tests and colonoscopy) are evaluated.