Knowledge is a foundation of the public trust in physicians. Knowledge drives diagnosis, treatment, and the shared decision making central to health care. Assessment of medical knowledge has thus been a cornerstone of Board Certification since 1914, when the American Board of Ophthalmology developed the first Board examination. As ABFM rethinks its certification portfolio, it is appropriate to revisit the scientific rationale for assessment of knowledge. What follows frames the key questions and evidence that drive ABFM policy and describes next steps.