With major advances in biomedical science over the last 2 decades, the possibility of treating human disease at a genetic level has become a tantalizing possibility. As a result, a growing number of investigators are focusing on the development of techniques to deliver therapeutic genes into cells. The liver has been a model organ in the development of this gene transfer technology. This review focuses on the attributes and limitations of the current gene delivery systems that have been explored in the context of liver disease and highlights the obstacles that must be addressed before hepatic gene therapy becomes a clinical reality.