The transnasal transsphenoidal approach is the preferred route for removal of most lesions of the sella turcica. The concept of transnasal surgery traversing the sphenoid sinus to reach the sella has existed for nearly a century. A comprehensive historical overview of the evolution of transsphenoidal surgery has been reported previously. In the present vignette, the authors focus on transsphenoidal surgery in the early 1900s, particularly on the methods advocated by Harvey Cushing and Oskar Hirsch, two prominent pituitary surgeons who pioneered the transsphenoidal technique. Cushing championed the sublabial approach, whereas Hirsch was the master of the endonasal route. Coincidentally, both surgeons independently performed the submucous septal resection for the first time on June 4, 1910. Although Cushing's and Hirsch's approaches were predicated on the work of their predecessors, their transsphenoidal procedures became the two most popular techniques and, for future generations of pituitary surgeons, laid the foundation for modem transsphenoidal surgery. In this comparative analysis, the authors compare the operative nuances of the approaches of Cushing and Hirsch and describe the contributions of these pioneers to modern transsphenoidal surgery.