For the minority of patients with hepatocellular carcinoma (HCC), surgical or locally ablative therapies may offer the prospect of cure. However, the majority of patients present with advanced disease such that treatment with curative intent is no longer possible. For some of these patients, with good hepatic reserve and a patent portal venous system, chemoembolisation may afford a modest survival benefit. The remainder of patients are frequently treated with systemic therapies with palliative intent. This review aims to summarise the current systemic treatment approaches for HCC in the adjuvant and palliative setting before reviewing the evidence for novel therapies emerging in this field. At present there are a number of interesting therapeutic agents with potential activity in HCC. The challenge now is the design of clinical trials to optimally evaluate these agents.