Hepatic gene therapy may take advantage of many unique anatomic, histologic, cellular, and molecular characteristics of the liver. Initial strategies for hepatic gene therapy, like initial efforts toward gene therapy in general, focused on ex vivo methods for gene delivery. Monogenic and multifactorial disorders of cholesterol metabolism are also important targets for hepatic gene therapy as is infectious or autoimmune hepatitis and cirrhosis. Gene therapy may also be used for various liver-specific diseases including infectious hepatitis, autoimmune hepatitis, or cirrhosis. The liver, site of many essential metabolic and secretory functions, will be an important target for somatic gene therapy. The application of gene therapy to many rare diseases may be limited by the cost of developing, validating, manufacturing, and providing the products required for gene therapy. Several different methods for gene delivery to the liver have been shown to be feasible in animal experiments and in initial clinical trial.