Liver diseases including inherited metabolic disorders, chronic viral hepatitis, liver cirrhosis and primary and metastatic liver cancer constitute a formidable health problem because of their high prevalence and the important limitations of current therapies. Gene therapy, a procedure based on the transfer of therapeutic genes to tissues, has been used since the 1990s as a new approach to treating a number of incurable conditions. After a period of lights and shades recent success in treating several devastating diseases like inherited immune deficiency disorders, beta-thalassemia, or inherited blindness appear to herald a new era where gene therapy can be listed among standard therapy options for a wide variety of human conditions. In this review, we provide information illustrating the potentiality of gene therapy in the management of liver diseases lacking other effective therapies.