The microsurgical technique of transsphenoidal hypophysectomy performed with the dogs and cats positioned in sternal recumbency enables the treatment of Cushing's disease, independent of skull type, in a safe and effective manner. In dogs, the short-term survival rate after hypophysectomy is comparable to that after treatment with o,p'-DDD, whereas the recurrence rate in this period is lower. When the surgeon has gone through a learning curve, the results of the 1- to 3-year follow-up interval may be better than those after adrenocorticolysis with o,p'-DDD. CT enables assessment of localization and size of the pituitary before surgery. In general, dogs with Cushing's disease and normal-sized pituitaries or moderately enlarged pituitaries (up to 12 mm in diameter) are suitable candidates for transsphenoidal surgery. In dogs with larger pituitary tumors and tumor extension rostrally or caudally over the dorsum sellae, transsphenoidal debulking surgery may be only a palliative treatment. The main complications are postoperative hypernatremia, keratoconjunctivitis sicca, diabetes insipidus, and secondary hypothyroidism. In cats, special attention should be paid to closure of the soft palate. The neurosurgeon must be familiar with these complications so as to recognize them as early as possible and to treat them immediately and effectively. It is concluded that microsurgical transsphenoidal hypophysectomy in dogs and cats with Cushing's disease is an effective method of treatment.