Many patients and providers are aware that colorectal cancer (CRC) "runs in families." A patient with 1 first-degree relative with CRC has approximately twice the personal risk for CRC as a similar person without this family history. Colorectal cancer is the third most common type of cancer in the United States. When providers neglect to collect information on family history, they may fail to appropriately tailor recommendations for screening for CRC for many patients. This review considers the existing data and summarizes an evidence-based approach to the common clinical problem of how and when to implement screening for CRC in a patient with a family history of colonic neoplasia. The authors discuss the varying risks for CRC given the patient's age, health habits, and personal and family histories. In the context of a clinical case that focuses on the effect of a single affected first-degree relative, the authors weigh the risks and benefits of various screening alternatives and briefly address chemoprevention, genetic testing, and future directions in screening for CRC.