Thomas Willis established neurology as a distinct discipline and made significant original contributions to many related fields including anatomy, pathology, cardiology, endocrinology, and gastroenterology. He is most remembered for his work in elucidating the function and anatomy of the circle of Willis. Willis' accomplishments and research methods can be credited in large part to his unconventional medical education which did not include traditional teachings, but rather emphasized learning through clinical practice. Although Willis was not the first to describe the arterial circle, he was the first to describe its function and provide a complete, undisputed illustration through his own innovative use of dye studies. The Willis classification of cranial nerves was still in use over 100 years after its original description. He has also described several disease entities and named many brain structures. Willis' accomplishments in comparative anatomy and understanding the pathophysiology of various diseases through original multidisciplinary experimental work in a clinical setting reveal that he was a true pioneer in translational research.