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Foundational authors of detective fiction from Edgar Allan Poe onwards often used medical doctors and themes in their mystery plots. It's no coincidence that medicine and crime fiction share a vocabulary of clues, evidence, and diagnosis. The mystery genre was integrally tied to the rise of scientific medicine as a respected profession. Indeed, classic detective stories are practically propaganda for the scientific method, showing readers how the powerful tools of observation and inference can solve any problem. Over the course of the 20th century, not only doctors, but also psychologists, social scientists and historians adopted the authoritative stance of the detective in constructing or reconstructing facts. As we study Sherlock Holmes and his modern proteges, such as TV doctor Gregory House, we will analyze how "medical mystery" narratives can shape our thinking about problems and solutions in medicine. We will consider post-modern detective stories that offer alternatives to the "Holmsian" model for understanding the complex clinical realities of today.