Modern medicine is one of humankind’s greatest achievements. Yet medical errors and irreproducibility in biomedical research suggest something is amiss. Concerns have driven considerable and thoughtful critical analyses, but the apparent intransigence of these problems suggests a different perspective is needed. The perspective pursued in this book begins with the idea that the need for certainty in medical decision-making has been and remains the primary driving force in medical reasoning. Faced with the unique challenges of having to treat the individual patient, the great variety of manifestations across patients is daunting. Either there are as many different “diseases” as there are patients, or there is some economical set of principles and facts that can be combined to explain each patient’s disease. Modern allopathic medicine follows from the presumption that economical sets of principles and facts exist. The challenge is to discover those principles and facts and develop means to reason from them to the individual patient in a way that provides certainty. Medical reasoning implicitly evolved from variations of logical deduction and induction reflected in the hypothetico-deductive, pattern recognition, and intuitive approaches used in medicine today. However, these require the judicious use of logical fallacies that increase utility but at the cost of certainty. Similarly, medical research necessarily requires the judicious use of a variation on syllogistic deduction. Their necessary use creates risks for errors. Many problems in medical reasoning and research are the consequence of injudicious uses. This book is a critical and historical analysis of medical reasoning from this perspective.