Cushing’s disease (CD) is rare (3/million/year) and due to autonomous pituitary ACTH hypersecretion, generally associated with a pituitary tumour (corticotropinoma). Genetic studies, initially published in 2014, established that ≥40% of corticotropinomas have a causative mutation of the ubiquitin-specific- protease 8 (USP8) gene that plays an important role in regulation of the epidermal growth factor receptor. First line treatment for CD in usually surgical, with success rates of 50-80% depending on tumour size and invasiveness and surgical expertise, but subsequent relapse occurs in 20-30%. Hence long term surgical cure of CD may ensue in only approximately 50% of patients. Adjunctive reoperation and/or pituitary irradiation have varying individualized successes. Final long term cure of CD can be achieved definitively by bilateral adrenalectomy, but with permanent primary adrenal insufficiency which entails risks of chronic reduced well-being and adrenal crises. Accordingly, there is a need for medical therapy for CD. Recently there is a substantial continuing effort to define the extent of effectiveness of traditional CD medical therapies, the adrenal steroidogenesis inhibitors, particularly ketoconazole and metyrapone as assessed by large retrospective databases and the newer pituitary active options, Pasireotide and Cabergoline, as well as the glucocorticoid receptor blocker, Mifepristone. Despite a background of numerous abandoned options in past decades, there are now a range of newer agents in various stages of development which either modify existing options or exploit new targets in pituitary tumours or on ACTH action. These newer agents promise sufficient safety and durable efficacy to allow medical therapy for CD to assume a greater role, with earlier use and reduction in the substantial long term metabolic and neurocognitive morbidity associated with CD.