Over the past century pituitary surgery has undergone multiple revolutions in surgical technique and technological advancements that have resulted in what is now recognized as modern transsphenoidal surgery. Although the procedure is well established in the current neurosurgical literature, the historical maze that led to its development continues to be of interest because it allows us to appreciate better the unique contributions made by the pioneers of the technique as well as the innovative spirit that continues to fuel neurosurgery. The early events in the history of transsphenoidal surgery have already been well documented. Therefore, the authors summarize the major early transitions along the timeline and then further describe more recent advancements in transsphenoidal surgery such as the surgical microscope, fluoroscopy, endoscopy, intraoperative neuroimaging, frameless image guidance, and radioimmunoassay. The story of these innovations is unique because each was developed as a response to certain needs of the surgeon. An understanding of these more recent contributions coupled with the early history provides a more complete perspective on modern transsphenoidal surgery.