Craniopharyngiomas represent one of the most challenging brain tumors to treat. In recent years, minimally invasive keyhole approaches have been increasingly used to remove these sellar, suprasellar and parasellar lesions. Of these approaches, the two most commonly used are the extended endonasal transsphenoidal route and the supraorbital eyebrow craniotomy. Although both approaches may be appropriate for a given patient, in many cases one route offers a better opportunity for safe and maximal tumor removal. Based on our combined experience using the endonasal and supra-orbital approaches for craniopharyngiomas, the endonasal route is preferred for removal of most retrochiasmal craniopharyngiomas and those lesions that are predominantly sellar in location. In contrast, those tumors that are predominantly prechiasmal or with prominent lateral extensions (a minority of craniopharyngiomas), the supra-orbital route is recommended. In some complex tumors with both prechiasmal and retrochiasmal extensions, either route may be appropriate. An additional key factor is surgeon experience with these keyhole approaches and conventional approaches. Compared to conventional larger craniotomies, the major limitation of both the endonasal and supraorbital approaches is a narrow surgical corridor. The endonasal approach has the added challenges of restricted lateral access, a greater need for endoscopy as well as a more demanding skull base repair. Herein, we review in this chapter the use of the supraorbital and endonasal approaches and summarize tumor and patient characteristics that help determine the optimal surgical route.