Introduction: Traditional systemic therapies offer limited benefit for advanced cancers of the liver. Immune checkpoints are inhibitory regulators of the immune system and the success of immune checkpoint inhibitors (ICIs) in the treatment of other cancers has led to clinical trials investigating the use of ICIs alone or in combination with other therapies for liver cancers.Area Covered: Clinical trials involving ICIs for the treatment of liver cancer were broadly reviewed. Hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastatic disease to the liver were covered. Phase I/II trials were prioritized, and relevant phase III trials were discussed. MEDLINE, PubMed, ASCO meeting library, and Web of Science databases were searched with the keywords 'immune checkpoint inhibitor' and 'targeted therapy' in combination with 'hepatocellular carcinoma', 'intrahepatic cholangiocarcinoma', and 'liver metastasis'. Major outcomes were safety and efficacy defined by response rate, progression-free survival, or overall survival.Expert Opinion: ICIs can improve progression-free and overall survival among patients with advanced disease with an acceptable safety profile. Given the heterogeneity of liver disease, ideal strategies will likely include a combination of ICI with additional therapies to achieve the most robust and durable response. Additional biomarkers will be needed to guide combination therapy to personalize treatment regimen for patients with primary and secondary liver cancers.