Cushings syndrome is a fascinating clinical challenge, both for diagnosis and management. Despite being a rare disease, it has many causes consisting of a broad variety of tumors. These tumors can arise from different tissues (i.e. pituitary, adrenal, lung…) varying from small benign and even non detectable tumors, to large aggressive cancers. The secretory spectrum of these tumors is broad qualitatively and quantitatively. It results from the molecular alterations that accumulate and participate in the tumor development, determining the differentiation of the tumor cells. This last decade, genomics led to spectacular progress in the identification of genetic and epigenetic alterations of many type of tumors causing Cushings syndrome. This allows now to depict the landscape of the genetic and epigenetic alterations of these tumors. This help to understand the major determinants of the different tumors types, their secretory capacity and their growth. For instance benign adrenocortical tumors (adenomas or micronodular adrenal hyperplasia) due to germline or somatic defect of main component of the cAMP pathway (i.e. PRKACA, PRKAR1A…) are small benign tumors causing overt Cushing. Inactivating germline mutations of ARMC5, identified by a combined genomic approach in Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH), cause benign large multiple adrenocortical tumors, containing very few chromosomal alterations and responsible for moderate cortisol excess. Integrated genomics of adrenocortical cancer (ACC) identified recurrent multiple alterations in driver genes linked to different gene expression, chromosomal and methylation profiles. This molecular classification of ACC is strongly associated with tumor outcome, allowing new molecular tools for prognostication. Somating mutations of USP8 identified by exome analysis are observed in a specific sub-group of pituitary corticotroph tumors causing Cushing disease. The molecular classification resulting from genomics studies clearly help to better understand the heterogeneity of the various causes of Cushing syndrome, supporting an individualized approach and new treatments.