Introduction: The treatment of unresectable hepatocellular carcinoma (HCC) has 
radically changed after the approval of the combination of atezolizumab plus 
bevacizumab as first-line treatment. A strong preclinical rationale exists to 
support the combination of bevacizumab, an anti-vascular endothelial growth 
factor monoclonal antibody (mAb), and atezolizumab, an anti-programmed death 
ligand 1 mAb. The efficacy of the combination was first assessed in the phase Ib 
GO30140 study, and the combination was then proven superior to the prior 
standard of care, sorafenib, in the phase III IMbrave150 trial.Areas covered: 
This article focuses on the mechanism of action of atezolizumab and bevacizumab, 
their synergistic action, and the two clinical trials leading to approval. We 
also collected the body of post-hoc analyses and meta-analyses to help guide the 
decision-making process in terms of patient selection and subsequent 
treatments.Expert opinion: Atezolizumab plus bevacizumab are the current 
standard of care for first-line treatment of unresectable or metastatic HCC and 
treatment-naïve patient should be treated with the combination, unless 
contraindications to the drugs. Since all the available agents for further lines 
of treatment have been approved for sorafenib-pretreated patients, prospective 
trials, post-hoc analyses, and real-world data assessing valid treatment 
sequencing are strongly needed.