Purpose Hepatocellular carcinoma is a heterogenous group of disease with a spectrum of disease presentations that developed on the setting of liver cirrhosis, although the achievements made in the imaging techniques have enabled the early diagnosis in nearly 60% of the cases in cirrhotic patients. However, hepatobiliary centers and tertiary liver transplant centers have to treat patients with advanced hepatocellular carcinoma with portal venous tumor thrombosis. Methods In this review, liver transplantation results in hepatocellular carcinoma patients with portal vein tumor thrombosis is reviewed. Results Although historically portal venous tumor thrombosis is considered a contraindication for radical surgical procedures such as liver transplantation, current data suggests that patients with hepatocellular carcinoma and macrovascular invasion can achieve favorable outcomes with liver transplantation provided that strict selection criteria is applied. One of the cornerstones of treatment of these patients is development of locoregional therapy such as transarterial chemo and radioembolizations. Transarterial radioembolization is effective in patients if the pretreatment liver failure is mild and the tumor burden including extension to the portal vein is low. Although data is lacking especially radioembolization could even help physicians to differentiate tumors with favorable biologic characteristics. Conclusions Therefore, these patients should be subject of multimodality treatment, and liver transplantation should be offered whenever objective and significant response is obtained by locoregional therapies.