The increasing use of endonasal techniques and a new 3-dimensional CT-guided imaging system have allowed us to develop a combined, minimally invasive endonasal approach to the pituitary gland. Thus far, more than 30 patients have undergone an endonasal transsphenoidal approach to the sella using a combined endoscopic approach, with additional selective use of the Instatrak CT-guided imaging system for real-time imaging. Our current technique involves obtaining a preoperative CT using a plastic head frame with registration markers. By using this head frame intraoperatively, real-time localization with CT images in axial, coronal, and sagittal planes can be performed. Using endoscopic techniques and a Papavero-Caspar speculum, the sella is exposed. A combined approach using endoscopes, the operating microscope, and real-time localization is undertaken to expose and resect tumors. We have encountered minimal associated complications in our series, and this method has been progressively modified to improve exposure and safety. Because we are able to visualize the sella without a sublabial incision or septal resection, we have nearly eliminated the need for nasal packing, reduced the average hospital stay to 2.5 days, and improved patient satisfaction.