Hepatocellular carcinoma (HCC) and hepatic metastases of colon cancers are malignant conditions of the liver that cause significant morbidity and mortality worldwide. Experimental models suggest that both conditions are characterized by epithelial-mesenchymal transition (EMT). Whilst ongoing research efforts aim to definitively clarify its role in human cancer patients, data from experimental models have unraveled a number of potential therapeutic targets as well as markers of prognostic importance. This area of research is generating intense interest amongst both basic scientists and clinicians. Some questions have been answered, but many important issues remain unresolved. We expect that in the near future, studies of human tissues can definitively clarify the role of EMT in the development and progression of human malignant diseases of the liver and that further studies can be carried out to determine how best to target aspects of the process for the treatment of patients with hepatocellular carcinoma and hepatic metastases of colon cancers.