AbstractAdrenocortical carcinoma (ACC) is a rare, heterogenous and highly malignant disease. Management of ACC is dependent on disease stage with complete surgical resection as the only potentially curative option. However, advanced, un-resectable, metastatic stages and also recurrences often require systemic treatments, which are unfortunately nowadays still unsatisfactory. The scarcity of preclinical models reflecting patient heterogeneities and furthermore drug-resistant phenotypes, has hampered the progress and development of new therapies in recent years. In this review, we provide an overview on the classical models and substantial progress which has been made over the last years in context of this aggressive disease.