The 2013 NCCN Clinical Practice Guidelines in Oncology for Colorectal Cancer Screening address the evaluation and management of patients at risk of inherited susceptibility to colorectal cancer. These patients include the 2 broad categories of patients with familial adenomatous polyposis and its variants, and those with hereditary nonpolyposis colorectal cancer, or Lynch syndrome. This article provides a somewhat personal, yet hopefully evidence-based, approach to the questions of when to test individuals for inherited susceptibility, and how to do so. "When" can be taken to mean "under what circumstance" and "at what age"; this article attempts to speak to each sense of the term.