Many efforts have been devoted to the development of gene therapy for primary liver tumors. This has been hampered by the absence of efficient gene transfer vectors for delivering genes into hepatoma cells in vivo. Also it remains to determine which type of gene has to be used to achieve complete tumor regression. Recent studies have documented improvements obtained using recombinant adenoviral vectors carrying the herpes simplex virus thymidine kinase gene as well as the ability to specifically target gene expression into the tumor cells by using the alpha-fetoprotein gene regulatory sequence. Therefore it seems reasonable to expect the development of clinical protocols in the near future.