A case of possible recurrent Cushing's disease (CD) is presented and data on current definitions of CD remission, persistence, and recurrence are reviewed. While prevailing guidelines recommend the use of serum cortisol in the first post-operative week for defining initial remission and predicting sustained remission, with the use of 24 h urinary free cortisol measurements if serum cortisol values are equivocal, there is debate as to which methods and thresholds best define CD remission and predict successful outcomes. Other methods used to define remission (and hence persistence and recurrence) include restoration of cortisol suppression after dexamethasone and physiologic diurnal cortisol rhythm as measured by midnight salivary free cortisol. However, the number and degree of abnormal test results needed to define recurrence, and the determination of which biochemical test has more significance when there are discrepancies between markers is inconsistent among studies. Further inquiry is warranted to examine if patients in apparent CD remission who have subtle hypothalamic pituitary adrenal (HPA) axis abnormalities represent distinctive remission subtypes versus mild or early recurrence. Additional investigation could also explore the degree to which these HPA axis abnormalities, such as alterations in cortisol circadian rhythm or partial resistance to dexamethasone, are associated with persistence of CD morbidities, including neuropsychiatric impairments, alterations in body composition, and cardiovascular risk.