The expanded endonasal approach provides access to the entire ventral skull base for resection of neoplasms involving the skull base and brain. The creation of large defects of the bone and dura endoscopically presents unique reconstructive challenges. A layered reconstruction of the dura with inlay and onlay fascial grafts covered with fat grafts is an effective technique for repair. An intranasal balloon catheter is used to provide counterpressure in the early phase of healing and a lumbar spinal drain is a useful adjunct in patients at increased risk of a cerebrospinal fluid leak. Vascularized flaps may be necessary in some patients receiving radiation therapy. Continued advances in surgical technology and the introduction of new biomaterials will facilitate the reconstruction of skull base defects following endonasal brain surgery.