Colorectal cancer is an ideal target for population screening—it is a prevalent disease that can be detected and treated at an asymptomatic stage leading to reduced cancer mortality. Several randomized clinical trials have demonstrated mortality benefit from different screening strategies.1 With this backdrop, the National Colorectal Cancer Roundtable has announced an ambitious effort to increase to 80% the proportion of the eligible US population who are up to date with screening by the year 2018.2 However, there are multiple options available for colorectal cancer screening that vary in accuracy, interval, and harms. There is also large variation in the quality of evidence to support different tests’ effectiveness to reduce cancer mortality and substantial differences in costs. When health care outcomes among competing strategies are unclear, recommendations developed through rigorous methods such as those used by the US Preventive Services Task Force (USPSTF) may assist clinicians, patients, and payers to make informed decisions.