Adrenocortical carcinoma (ACC) is a heterogeneous neoplasm with an incompletely understood pathogenesis and an unsatisfactory prognosis. However, international initiatives like the European Network for the Study of Adrenal Tumours (ENSAT) and international trial consortia recently led to improved diagnosis and treatment. Activated signalling pathways primarily involved in adrenal development like IGF2, SF1, and β-catenin pathways play also a key role in the ACC development and provide important diagnostic and prognostic information. A standardized comprehensive diagnostic work up is now recommended by ENSAT (www.ensat.org/ACC.htm). A major diagnostic advance is 18F-FDG-PET, as virtually all ACC patients demonstrate high uptake leading to high diagnostic sensitivity. In addition, 11C-metomidate or 123I-iodometomidate tracers bind selectively to CYB11B enzymes thereby conferring high specificity to ACC imaging. Survival in ACC is highly stage dependent with the new ENSAT staging system providing superior prognostic information compared to the WHO/UICC system. Surgery aiming at R0 resection remains the treatment of choice and requires an experienced surgeon. Smaller ACCs (diameter <9 cm) may be removed safely by minimal invasive surgery. To establish an adequate basis for treatment decisions pathology reports should include the Weiss score, resection status (R0, R1, and R2) and the Ki67 proliferation index. After complete resection most patients benefit from adjuvant mitotane. Depending on the individual risk adjuvant radiation therapy of the tumor bed may be added. Cytotoxic drugs (including platinum compounds) will be added to mitotane in advanced disease. Results of the international FIRM-ACT trial, the largest ever trial in patients with advanced ACC, will become available in early 2011 and will establish a benchmark therapy. New targeted therapies (e.g. IGF1 receptor antagonists, 131I-iodometomidate) are under investigation and may soon lead to improved treatment options. Furthermore, the recently funded (FP7 program) ENSAT-CANCER consortium holds great promise to keep the recently gained momentum in ACC research.