Three significant factors in the shaping of modern medicine contribute to broad perceptions about trust in the patient-physician relationship: moral, professional, and epidemiological uncertainty. Trusting a physician depends first on trusting a person, then trusting a person's skills and training, and finally trusting the science that underwrites those skills. This essay, in part based on my book, Trusting Doctors: The Decline of Moral Authority in American Medicine (Princeton University Press, 2008), will address the forms of uncertainty that contribute to the nature of difficult encounters in the patient-physician relationship.