OBJECTIVES: The objective was to examine the evidence on the efficacy of current treatments in patients with Cushing’s disease (CD) to support healthcare decision-making.  METHODS: A systematic literature search using predefined strategy was performed in the Cochrane library, EMBASE, PUBMED and MEDLINE to identify observational studies in North America and Europe from 2003 to 2013. A total of 32 studies were included and analyzed, out of 791 studies found.  RESULTS: For primary CD (n=23/32), transsphenoidal surgery (TSS) remains the procedure of choice (n=20/23, 87% of studies). For recurrent/persistent disease (n=11/32), treatment received was; TSS in 36.3%, radiotherapy in 27.35%, bilateral adrenalectomy (BLA) in 18.2% and medical therapy in 18.2%. Remission rates post primary TSS were 65%-91% with recurrence of 5%-24%. Variability in remission rate could be attributed to the lack of uniformity in the definition for remission, different length of follow-up, patient population (macro- vs. micro-adenomas), surgeon experience and the type of TSS technique used (endoscopic vs. microscopic). Remission rate was lower for recurrent/persistent CD (37.5%-71%).Major complications were; diabetes insipidus (6%-40% transient, 0%-12.5% permanent), cerebrospinal fluid leak (1%-83%) and hypopituitarism (0%-79%). Radiation therapy appeared effective for secondary treatment (remission rate 48% vs. 27% for primary CD) with benefits observed in the long-term. Side effect was hypopituitarism (0%-75%). Main secondary treatment was BLA with success rate of 100% in reversing hypercortisolism. Complications included Nelson’s syndrome and lifelong need for corticosteroids replacement. Two studies were retrieved that evaluated efficacy of ketoconazole and cabergoline in small patient populations, 38 and 20 patients respectively. Combination of pasireotide, cabergoline and ketoconazole achieved response in 88% after 80 days. CONCLUSIONS: TSS remains the appropriate treatment for primary CD.  However, there appears to be lower success rates and significant complications in patients with persistent/recurrent disease.