To meet the need for qualified anesthetists, American surgeons recruited nurses to practice anesthesia during the Civil War and in the latter half of the 19th century. The success of this decision led them to collaborate with nurses more formally at the Mayo Clinic in Minnesota. During the 1890s, Alice Magaw refined the safe administration of ether. Florence Henderson continued her work improving the safety of ether administration during the first decade of the 20th century. Safe anesthesia enabled the Mayo surgeons to turn the St. Mary’s Hospital into a surgical powerhouse. The prominent surgeon George Crile collaborated with Agatha Hodgins at the Lakeside Hospital in Cleveland to introduce nitrous oxide/oxygen anesthesia. Nitrous oxide/oxygen caused less cardiovascular depression than ether and thus saved the lives of countless trauma victims during World War I. Crile devised “anoci-association,” an outgrowth of nitrous oxide/oxygen anesthesia. Hodgins’ use of anoci-association made Crile’s thyroid operations safer. Pioneering East Coast surgeons followed the lead of the surgeons at Mayo. William Halsted worked closely with Margaret Boise, and Harvey Cushing worked closely with Gertrude Gerard. As medicine became more complex, collaboration between surgeons and nurse anesthetists became routine and necessary. Teams of surgeons and nurse anesthetists advanced thoracic, cardiovascular, and pediatric surgery. The team of Evarts Graham and Helen Lamb performed the world’s first pneumonectomy. Surgeon-nurse anesthetist collaboration seems to have been a uniquely American phenomenon. This collaboration facilitated both the “Golden Age of Surgery” and the profession we know today as nurse anesthesia.