Evidence-based medicine (EBM) emerged during the 1990s as a new approach to clinical practice informed by medical research, with a focus on evidence from randomized controlled trials (RCTs) and systematic reviews of RCTs. This chapter gives an account of EBM and its epistemological and ethical justifications, together with key critiques. EBM relies upon epistemological claims about the ability of RCTs to eliminate certain forms of bias and to establish whether there is a causal relationship between an intervention and an outcome. Epistemological critiques of EBM include concerns about whether EBM can “prove” causation, the rejection of mechanistic models of causation, applying the results of RCTs to individual patients, and whether EBM has in fact benefitted patients and healthcare systems. The ethical justifications for EBM include its promise of better patient outcomes through better informed clinicians and the idea that public health policy based on EBM can support equity and minimize waste of resources. Ethical critiques of EBM note that despite its potential for reducing particular forms of bias, the research upon which EBM is based is often industry funded, creating conflicts of interest that are associated with new sources of bias. In the face of these concerns, EBM is under pressure to reestablish its credibility. The chapter ends by noting how EBM is challenged by and must evolve in response to new forms of data and new analytic tools.