Periodic screening of people at average risk for colorectal cancer (CRC) is recommended by three important national guideline groups, the United States Preventive Services Task Force (USPSTF), the American Cancer Society (ACS), and the U.S. Multi-Society Task Force on Colorectal Cancer (MSTF), as well as multiple professional societies. For CRC screening to contribute to a reduction in CRC mortality without unreasonable harms and costs, however, it must be offered to people who have a reasonable probability of net benefit, and it must be conducted effectively and efficiently. These issues of use and quality are especially salient for CRC screening because it is in some ways more complex (e.g., variation in timing and types of tests, invasiveness of most tests) than other screening programs. Underuse of CRC screening has been a clear problem for some years; evidence is now growing that overuse (i.e., screening people with little potential for net benefit) and misuse (i.e., conducting screening in ways that reduce net benefit) may also be important problems. This report is a systematic review of evidence about the use and quality of screening for CRC focusing on four primary key questions (KQs). It also includes an initial background section (KQ 1) on trends and the current situation of use and quality, and it presents a concluding discussion on needed research (KQ 6). The specific KQs of interest were as follows: KQ 1. What are the recent trends in the use and quality of CRC screening? KQ 2. What factors influence the use of CRC screening? KQ 3. Which strategies are effective in increasing the appropriate use of CRC screening and followup? KQ 4. What are the current and projected capacities to deliver CRC screening and followup at the population level? KQ 5. What are the effective approaches for monitoring the use and quality of CRC screening? KQ 6. What research is needed to make the most progress and have the greatest public health impact in promoting the appropriate use of CRC screening?