Liver cancer is the sixth most common cancer, killing 600,000 people each year worldwide. Hepatocellular carcinoma (HCC) is the most common form of liver cancer. HCC has several specific features. In particular, the risk factors and causes are well known, thereby permitting - in theory - primary prevention and early detection surveillance programs. Also, HCC is a vascular solid tumor with a high degree of drug resistance (the so-called angiogenic and MDR phenotype). These features should be targeted primarily, if not exclusively, by future biological therapies. In this review, the authors report the most recent therapeutic developments, including emerging targeted strategies.