Primary and metastatic neoplasms of the liver account for more than a million deaths per year worldwide. Despite decades of research, effective novel therapies for these cancers are urgently needed. Oncolytic virotherapeutics represent a novel class of pharmacophore that holds promise for the treatment of hepatic neoplasms. Cancer-specific replication is followed by oncolysis, virus spreading and infection of adjacent cancer cells. This process is then repeated. Virotherapeutics target multiple genetic pathways involved in carcino-genesis, and demonstrate activity against apoptosis-resistant tumour cells. This platform can also exploit the advantage of multiple intrinsic anti-cancer therapeutic mechanisms, combining direct viral oncolysis with therapeutic transgene expression. Recent advances in pre-clinical and clinical studies are revealing the potential of this unique therapeutic class, in particular for liver cancers. This review summarizes the available data on applying oncolytic virotherapeutics to hepatic neoplasms to date, and discusses the challenges and future directions for virotherapy.