The treatment of advanced hepatocellular carcinoma has been challenging for a long time. Cytotoxic chemotherapeutic agents were generally too toxic for these patients, and their tumor responses were disappointedly low. Sorafenib, the first drug proven to provide survival benefit for patients with advanced hepatocellular carcinoma, has shed a light into the treatment of this disease. However, the low response rate and limited survival prolongation of sorafenib left much to be improved. In recent years, the development of clinical trials for advanced hepatocellular carcinoma is booming. Despite some promising preliminary results, the therapeutic benefit of these novel targeted agents should be confirmed in phase III trials.