For more than a decade, systemic treatment of advanced hepatocellular carcinoma (HCC) remained limited to the use of the tyrosine kinase inhibitor sorafenib, with lenvatinib being a non-inferior alternative to this standard of care. Recently, however, results of the phase III IMbrave 150 trial, demonstrated that the combination of atezolizumab and bevacizumab is associated with a significantly better progression-free and overall survival than sorafenib in the frontline treatment of patients with advanced HCC. This finding will have a dramatic impact on the treatment paradigm for these patients. In addition to atezolizumab-bevacizumab, several other immunotherapy-based treatment regimens are being evaluated in the treatment of advanced HCC.