The multikinase inhibitor sorafenib, which inhibits targets related to tumor cell proliferation and angiogenesis, was the first systemic agent to demonstrate a significant improvement in the overall survival for patients with advanced hepatocellular carcinoma (HCC) in two large randomized controlled Phase III trials. Together with its manageable safety profile (mainly diarrhea, hand-foot skin reaction and fatigue), sorafenib was approved for the treatment of patients with (unresectable) HCC in 2007. Since then, sorafenib has been established as the standard of care in Child-Pugh A patients with advanced HCC or in those ineligible for or after failure of locoregional therapies in the intermediate stage of the disease. This article summarizes current knowledge and future perspectives regarding the use of sorafenib in patients with HCC.