These words penned by John Keats, who was a physician as well as a poet, remind us of the human struggle to live in a grayscale space where uncertainty is rife—a space that is neither black nor white. Our quest for certainty is central to human psychology, however, and it both guides and misguides us. Although physicians are rationally aware when uncertainty exists, the culture of medicine evinces a deep-rooted unwillingness to acknowledge and embrace it. Embodied in our teaching, our case-based learning curricula, and our research is the notion that we must unify a constellation of signs, symptoms, and test results into a solution. We demand a differential diagnosis after being presented with few facts and exhort our trainees to “put your money down” on a solution to the problem at hand despite the powerful effect of cognitive biases under these conditions. Too often, we focus on transforming a patient’s gray-scale narrative into a black-and-white diagnosis that can be neatly categorized and labeled. The unintended consequence—an obsession with finding the right answer, at the risk of oversimplifying the richly iterative and evolutionary nature of clinical reasoning—is the very antithesis of humanistic, individualized patient-centered care. We believe that a shift toward the acknowledgment and acceptance of uncertainty is essential—for us as physicians, for our patients, and for our health care system as a whole. Only if such a revolution occurs will we thrive in the coming medical era. In medicine today, uncertainty is generally suppressed and ignored, consciously and subconsciously. Its suppression makes intuitive sense: being uncertain instills a sense of vulnerability in us—a sense of fear about what lies ahead. It is unsettling and makes us crave black-and-white zones, to escape this gray-scale space. Our protocols and checklists emphasize the black-andwhite aspects of medicine. Doctors often fear that by expressing uncertainty, they will project ignorance to patients and colleagues, so they internalize and mask it. We are still strongly influenced by a rationalist tradition that seeks to provide a world of apparent security. Yet the reality is that doctors continually have to make decisions on the basis of imperfect data and limited knowledge, which leads to diagnostic uncertainty, coupled with the uncertainty that arises from unpredictable patient responses to treatment and from health care outcomes that are far from binary. Key elements for survival in the medical profession would seem, intuitively, to be a tolerance for uncertainty and a curiosity about the unknown. Have we created a culture that ignores and denies that requirement? Could our intolerance of uncertainty, in turn, be contributing to the accelerating rates of burnout and the rising cost of health care? For there is no doubt that absolute truth and certainty are hard to come by in clinical medicine.