Hepatocellular carcinoma (HCC) is a highly prevalent and lethal neoplasia. Several studies have shown that HCC is the main cause of death in patients with cirrhosis. A better knowledge of the natural history of the tumor and the development of staging systems has allowed to refine the prognosis of the patients. The Barcelona Clinic Liver Cancer system (BCLC) has become the preferred staging system since it takes into account the tumor characteristics, the degree of liver impairment and the physical performance. It has been endorsed by several scientific associations and research consortia as it does not just define prognosis, but, more interestingly, it links staging with prognosis assessment and treatment recommendation. Curative therapies such as resection, transplantation and ablation can improve survival in patients diagnosed at an early HCC stage and may offer a long-term cure with overall survival that may exceed 70% at 5 years. Patients with intermediate stage HCC benefit from chemoembolization and proper selection of candidates permits a 50% survival at 3-4 years. Finally, patients diagnosed at an advanced stage benefit from sorafenib, an oral available, multikinase inhibitor with antiangiogenic and antiproliferative effects. Current research efforts are aimed at further refining prognosis prediction through molecular profiling and enhanced clinical characterization. At the same time, better knowledge of the molecular mechanisms of cancer should result in a further improvement of the current life expectancy of patients.