At the center of the COVID-19 pandemic lies a ubiquitous feature of medicine. Medicine is permeated with ignorance. Seizing this moment to assess the current state of medical sociology, this article articulates a sociology of medical ignorance. We join insights from earlier medical sociological scholarship on uncertainty with emerging research in the sociology of ignorance to help make sense of the omnipresent but sometimes invisible dynamics related to the unknowns in medicine. Then we examine two streams of inquiry with a focus on uncertainty and ignorance—(1) research on the interconnections between technology, medical authority, and ignorance and (2) research on lay expertise within the context of ever-present uncertainties. For decades, and to good effect, medical sociologists have asked, “What does medicine know, and what are the consequences of such knowing?” Going forward, we encourage medical sociologists to examine the unknown in medicine and the consequences of not knowing. © American Sociological Association 2021.