The management of hepatocellular carcinoma (HCC) has greatly improved following standardization of the therapeutic algorithms and establishment of evidence-based criteria for prognostication (BCLC staging). Patients with an early-detected cancer (<5 cm in size) in a well-compensated liver (BCLC-A) represent the best prognostic subgroup, with an expected 5-year survival of up to 75% following radical therapies, including transplantation, resection, and percutaneous ablation. The best prognostic groups for liver transplantation are patients within the radiological Milan criteria, whereas for patients undergoing limited hepatic resection, prognosis depends on the degree of portal hypertension and biochemical derangement of the liver. Patients with biochemically compensated cirrhosis, low portal hypertension, and a single <2 cm HCC nodule may have comparably high survival rates by local tumor ablation with alcohol or radiofrequency and with hepatic resection. The latter, however, is more effective than ablation in patients with HCC nodules between 2 and 5 cm in size, whereas radiofrequency ablation is superior to alcohol injection in 3–4 cm tumors due to better control of local recurrence. Transhepatic arterial chemoembolization is the standard of care for patients with an intermediate tumor (BCLC-B): it prolongs patient survival from 16 to 20 months, on average. Survival of patients with advanced HCC (BCLC-C) is prolonged by treatment with the multikinase inhibitor sorafenib: this drug has therefore become the standard of care for patients with an advanced HCC and stable liver function. Multimodality treatments are an option for any treatable stage of HCC: however, these are of unproven value. The fourth stage (BCLC-D) includes patients with an average survival of 6 months: these should be given supportive care only. In the near future, prognostication based upon genetic fingerprints of the tumor may change the therapeutic scenario, thereby fulfilling an important unmet therapeutic need.