We wrestled for a long time with the question of whether to include the term “evidence-based” in the title of the first edition of this book. Although both of us are firm believers in the principles and goals of evidence-based medicine (EBM), as articulated by its first proponents we also knew that the term “evidence-based” would be viewed negatively by some potential readers [2–4]. We decided to keep “evidence-based” in the title and use this chapter to directly address some of the criticisms of EBM, many of which we believe have merit. We also recognize that, as elegant and satisfying as evidence-based diagnosis is, there are some very real cognitive barriers to applying it in a clinical setting. These barriers are the second topic of this chapter. Finally, we end the book with some thoughts on the future of evidence-based diagnosis and why it will be increasingly important.