Despite evidence-based medicine’s (EBM’s) significant evolution and maturation from its revolutionary origins to its current form as the preeminent means of practicing medicine, there are still good reasons to be unsatisfied with EBM. This essay explores two important new developments in EBM: recently articulated accounts of the scientific basis of EBM, and the related writings of the GRADE Working Group to create standards for interpretation of the medical literature and evaluation of recommendations. A review of Karanicolas, Kunz, and Guyatt’s (2008) three-step articulation of EBM’s scientific basis demonstrates that the supposed soundness of each principle is not attributable to its scientific status; instead, the normative language of each principle highlights EBM’s grounding in an only partially articulated philosophical framework. The GRADE Working Group’s effort similarly relies on credibility, consensus, and trust in its defense and justification of EBM. These recent developments in EBM reveal that if the clinical research literature is to be informative or foundational to the enterprise of health care, much work needs to be done to secure its trustworthiness and integrity. An agenda for examining trust and trustworthiness in the context of health research is proposed.