This chapter aims to provide insightful guidance drawn from an updated litera ture search and the long experience of our multidisciplinary team in the surgical management of Cushing’s disease. We will first compare the two primary TSS tech niques—microscopic and endoscopic—emphasizing the importance of surgical expertise. We will also discuss new imaging modalities, which may improve the preoperative localization of corticotroph microadenomas. Addressing scenarios where extensive imaging fails to detect pituitary tumors, the chapter analyzes diag nostic challenges, offering guidance on improving localization and effective surgi cal strategies, including the contribution of neuronavigation systems and intraoperative MRI (iMRI). This comprehensive exploration aims to empower clini cians in managing the complexities of Cushing’s disease, from accurate localization to advanced surgical techniques and beyond.