We review the case of a young man who developed a constellation of symptoms and signs—bizarre behavior, seizures, abnormal movements, and autonomic instability—that evaded diagnosis at the time of presentation. We use this case to explore the way medical knowledge changes over time. Despite the dramatic advances in our understanding of neurological diseases in recent decades, physicians tend to approach diseases and diagnoses as if they were immutable. Our case reinforces how the diagnosis and treatment of disease are determined by an ever-changing historical context driven by the rapid expansion of medical knowledge. We discuss the implications of this realization and present strategies for navigating the boundaries of knowledge, both in practice and in principle.