Present treatment options for hepatocellular cancer (HCC) are limited to those individuals with good liver function and early stage disease. Unfortunately this includes only a minority of patients, few of which are actually cured of their cancer. Over the last 15-20 years biotechnology has made a very significant impact on medical research, to the extent that we know very much more about the regulation of normal cell growth and death, as well as the mechanisms underlying its disruption in disease processes. This knowledge has and is being rapidly exploited by academic and pharmaceutical organisations, often in collaboration. The result is the development, testing and steady introduction of therapies that target specific abnormalities in cancer cells. Although the safety and effectiveness of the majority of these agents has yet to be established in cirrhotic patients with HCC, we are hopeful that we will shortly see an increase in effective treatment options available for clinical use this disease. This review focuses on aberrant cancer proteins and pathways relevant to HCC, as well as the novel therapies or strategies targeting them, that are currently in the development or testing stages.