Sorafenib is thus far the only systemic treatment for hepatocellular carcinoma(HCC) based on the results of two randomized controlled trials performed in Western and in Eastern countries, despite a poor response rate(from 2% to 3.3%) following conventional evaluation criteria. It is now recognized that the criteria(European Association of the Study of the Liver criteria, modified response evaluation criteria in solid tumors) based on contrast enhanced techniques(computed tomography scan, magnetic resonance imaging) aimed to assess the evolution of the viable part of the tumor(hypervascularized on arterial phase) are of major interest to determine the efficacy of sorafenib and of most antiangiogenic drugs in patients with HCC. The role of alphafetoprotein serum levels remains unclear. In 2016, in accordance with the SHARP and the Asia-Pacific trials, sorafenib must be stopped when tolerance is poor despite dose adaptation or in cases of radiological and symptomatic progression. This approach will be different in cases of available second-line therapy trials. Some recent data(in renal cell carcinoma) revealed that despite progression in patients who received sorafenib, this drug can still decrease tumor progression compared to drug cessation. Then, before deciding to continue sorafenib post-progression or shift to another drug, knowing other parameters of post-progression survival(Child-Pugh class, Barcelona Clinic Liver Cancer, alphafetoprotein, post-progression patterns in particular, the development of extrahepatic metastases and of portal vein thrombosis) will be of major importance.