The evidence-based medicine (EBM) paradigm, introduced in 1992, has had a major and positive impact on all aspects of health care. However, widespread use has also uncovered some limitations; these are discussed from the perspectives of two clinicians in this, the first of a two part narrative review. For example, there are credible reservations about the validity of hierarchical levels of evidence, a core element of the EBM paradigm. In addition, potential and actual methodological and statistical deficiencies have been identified, not only in many published randomized controlled trials but also in systematic reviews, both rated highly for evidence in EBM classifications. Ethical violations compromise reliability of some data. Clinicians need to be conscious of potential limitations in some of the cornerstones of the EBM paradigm, and to deficiencies in the literature.