Adrenal cortical carcinoma is a relatively uncommon malignancy that represents a significant clinical challenge for the development of optimal treatment strategies. Historically, successful treatment has relied upon rapid identification of the lesion, accurate staging with diagnostic imaging, and complete surgical extirpation. Although the framework of a successful treatment paradigm still relies on these steps, advances in diagnostic imaging have led to increased accuracy in diagnosis, and advances in laparoscopic surgical technique have served to reduce morbidity for patients facing treatment. This review focuses on a discussion of advances in modalities for the diagnosis and treatment of adrenal cortical carcinoma amenable to curative therapy. Patients that present with metastatic or locally advanced disease generally are treated with mitotane-based chemotherapy with or without the addition of cytotoxic drugs. Contemporary results of this treatment approach are presented in this review as well as a discussion of further directions for the treatment of patients with advanced disease.