Cushing disease (CD) is hypercortisolemia caused by a pituitary tumor. The culprit sellar neoplasm is often too small to detect on neuroimaging, yet its size belies its immense potential morbidity. Modern care of these complex patients demands a dedicated team composed of neurosurgeons, otolaryngologists, and endocrinologists to navigate patients toward a cure. Diagnosis alone is a challenge as CD shares a similar phenotype of cortisol excess with several other disorders that can cause Cushing syndrome. Operative techniques and nuances aside, we summarize the pertinent endocrinologic foundation a neurosurgeon should possess to manage CD.