The critical and historical analysis of medical reasoning begins from the central importance of certainty in practice and research. The need for certainty manifests in preference for objective tests, particularly their overutilization, and evidence-based medicine used synonymously with randomized control trials. The variety of manifestations in each patient and each subject of research is a challenge to certainty. The response is a choice of epistemic perspectives. Either there are as many “diseases” as there are patients, or there is an economical set of diseases, defined by principles and facts, by which any patient can be understood. The latter suggests a type of logical deduction, and deductive logic is indeed the model. However, deduction, while providing certainty, does not generate new knowledge. Rather, derivative logical fallacies must be used that provide utility at the expense of certainty. Similarly, induction also is problematic. The implications of the conundrum and responses are introduced.