Abstract The development and differentiation of the adrenal cortex and the maintenance of normal functional zonation is effected by the interaction of classical hormones and local factors, such as growth factors and cytokines, produced by cortical and stromal cells and neurotransmitters released from the cortical plexus. Specific intracellular molecules are also important. Mutations in the genes encoding components of these pathways have now been demonstrated in a number of inherited adrenal diseases including congenital adrenal hyperplasia and hypoplasia. Similarly, molecular genetic analysis is helping elucidate other non-neoplastic cortical diseases such as glucocorticoid-suppressible hyperaldosteronism and primary pigmented nodular adrenocortical disease (PPNAD). It is becoming more important to be able to diagnose malignant potential in adrenal cortical tumours because cortical nodules are identified more commonly during scanning for the investigation of other intra-abdominal disease. Current approaches to histological analysis are outlined. Current research findings on which future diagnosis may be based are discussed.