Liver resection, transplantation, and local ablation are potential curative treatment options but can only be offered to patients with early stage hepatocellular carcinoma (HCC). Patients with macrovascular tumor invasion and extrahepatic metastases are candidates for palliative systemic therapies. Achieving radiological complete response can be associated with long-term remission and excellent outcome. However, despite recent advancements in the medical treatment of advanced stage HCC, complete remission with available systemic treatment options still remains a rare event. This review summarizes data on radiological complete response to systemic therapies and discusses issues that may complicate the goal of achieving cure in advanced stage HCC.