Oliver Wendell Holmes, Sr. was a physician, dean of the Harvard Medical School, one of the best regarded American poets of the 19th century, father of a future United States Supreme Court Justice, inventor and - unknown to many - an anatomist. His friends included Ralph Waldo Emerson, Henry Wadsworth Longfellow, and Louis Pasteur. He trained with some of the most influential anatomists/surgeons of his day including Lisfranc, Larrey, Velpeau, Bigelow, and Dupuytren. As a teacher of anatomy, he had strong feelings regarding medical curricular reform and to some, was considered one of the best lecturers in the discipline. As dean, he pioneered social reform by admitting both white women and free black men to Harvard Medical School. He coined the term "anesthesia," was the first American to introduce microscopy to a medical curriculum, and made important contributions to the understanding of the spread of infectious disease. Herein, we review the life of this influential American academic and focus on his contributions to the field of anatomy.