Relatively frequent, adrenal masses include a multitude of different tumor types: uni- or bilateral hyperplasias, adenomas, and the rare entity of adrenocortical carcinomas. With significant progress in our appreciation of their underlying molecular pathomechanisms and from analysis of affected individuals and their families, a number of inherited diseases and tumor syndromes have been linked to adrenocortical tumorigenesis. These syndromes and diseases include the Carney complex, the McCune-Albright syndrome, multiple endocrine neoplasia type 1, familial adenomatosis coli, congenital adrenal hyperplasia, familial forms of primary aldosteronism, the Beckwith-Wiedemann syndrome, and the Li-Fraumeni syndrome. The key to successful management of these syndromes is identification of patients harboring adrenal tumors within the context of hereditary diseases, since diagnostic procedures, therapy and follow-up may significantly differ from the management of sporadic, isolated adrenal tumors. This review explores the underlying genetic defects, diagnosis and therapy of the major heritable tumor syndromes associated with adrenocortical tumorigenesis.