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An old joke states that one need not worry about one's enemies, but may be in danger from one's friends. We review a number of "enemies" and "friends" of evidence-based medicine (EBM). To understand where these enemies and friends have come from, it is important to see how the rise of EBM has created shifts in power, especially within academic medicine. Attacks from "enemies"—especially the criticism that EBM amounts to overturning a medicine of the individual in favor of an undesirable population medicine—tend to reflect misunderstandings of EBM, or of the degrees of uncertainty inherent in medicine itself, rather than substantive criticisms. The activities of three categories of so-called friends might well give EBM an undesirable reputation. These "friends" are the practitioners of a crude version of EBM (uncritical acceptance of randomized controlled trials while rejecting all other forms of evidence), commercial sponsors of clinical trials whose biases distort the available evidentiary base, and bureaucrats who employ EBM practices in the service of inequitable rationing of health resources.