Adrenocortical carcinoma (ACC) is a malignant tumor that is associated with steroid hypersecretion in up to 60% of cases. The most common hypersecretion is cortisol, followed by androgens, while aldosterone and estrogens are less frequently secreted. It is key to identify hormonal excess in order to treat promptly potentially life-treating complications of endocrine syndromes. Hypercortisolism can present as a full-blown Cushing’s syndrome, with severe manifestations such as hypokalemia, increased risk of infections, thrombosis, diabetes and hypertension, which are resistant to treatment. However, hypercortisolism can also present as subclinical Cushing’s, without overt manifestations. Hypercortisolism is also a well-known negative prognostic factor even when ACC can be extirpated completely with resolution of cortisol excess. Treatment of full-blown Cushing’s syndrome should be specifically pursued with inhibitors of steroidogenesis (metyrapone, ketoconazole or osilodrostat) in many patients with advanced ACC in preparation for surgery or chemotherapy. These drugs may be combined with mitotane that needs time to become active. It is mandatory to specifically address the complications of hypercortisolism, such as hypokalemia, infections, hyperglycemia, thromboembolic events.