Hepatocellular carcinoma (HCC) is a serious malignancy with 21,000 new cases estimated for 2008. Several common diseases are associated with an increased risk of the development of HCC, including viral hepatitis, cirrhosis, and other chronic liver diseases. Most patients present with advanced disease, and therefore have only limited therapeutic options. However, advancements in screening and surveillance have allowed more patients to be identified and diagnosed with earlier-stage disease, increasing their therapeutic options. Several treatment modalities exist for early- and intermediate-stage disease, including ablative techniques and embolization methods. Additionally, advances in targeted therapy have resulted in the approval of the oral multitargeted tyrosine kinase inhibitor sorafenib, resulting in improved length of survival. In this roundtable discussion, the current epidemic of HCC is addressed, including factors contributing to an increased rate of occurrence. Additionally, the optimal screening and diagnosis of HCC patients is discussed, and the appropriate treatment modalities for each stage of HCC are presented.