The mechanisms of production of cortisol in adrenal Cushing's syndrome, in which corticotropin is suppressed, were previously unknown and believed to be autonomous. Increasing evidence indicates that adrenocortical steroidogenesis may be mediated by hormones other than corticotropin because of the aberrant (or ectopic, illicit) expression and function of their membrane receptors in the adrenal tumors. To date, ectopic receptors for gastric inhibitory polypeptide, β-adrenergic agonists, luteinizing hormone/human chorionic gonadotropin, and probably angiotensin II type 1 (AT-1) have been identified; altered activity of eutopic receptors such as those for vasopressin (V1-arginin-vasopressin receptor), serotonin (5-HT4R), and leptin may be involved. The identification of aberrant adrenal hormone receptors offers the potential for novel pharmacologic therapies by suppressing the endogenous ligands or by blocking the aberrant receptor with specific antagonists. Further studies may identify a larger diversity of hormone receptors capable of coupling to G-proteins, adenylyl cyclase, and steroidogenesis in adrenal tumors, and probably in other endocrine and nonendocrine tumors.