Central adrenal insufficiency (AI) represents a life-threatening disorder that results from a reduced cortisol production due to an impairment production of adrenocorticotropic hormone (ACTH). In particular, secondary AI results from pituitary disease that impedes the release of ACTH, while tertiary AI is caused from an impaired synthesis of corticotropin-releasing hormone. Central AI has an estimated prevalence of 150-280 per million, resulting more common than primary AI. Prompt diagnosis and management of this condition is crucial, but the diagnostic investigation can often be challenging, in particular in cases of recent onset of secondary adrenal insufficiency. Moreover, different formulations of steroid replacement therapy are available for both primary and central adrenal insufficiency, but the therapy of choice for the treatment of secondary hypoadrenalism is still debated. In particular, several data confirm the advantages of dual-release hydrocortisone formulation in primary hypoadrenalism, while data for secondary AI are still lacking. However, in spite of few clinical data, the use of dual release hydrocortisone can be extremely favorable in ACTH deficiency, which is associated with an increase of overall and cardiovascular mortality, also due to the risk of overtreatment. In this condition, the use of a modified-release glucocorticoid formulation, which has been demonstrated to improve metabolic profile, can be extremely attractive.