The liver plays a central role in many inherited and acquired genetic disorders, and thus is a potential target for nucleic acid therapies. Despite the great strides made in basic molecular biology over the last two decades successful gene therapy remains elusive. Most recently, there has been considerable effort to develop non-viral gene therapy approaches, in part, to overcome the potential complications associated with viral delivery systems. This review outlines the different non-viral approaches available to the liver, and includes a detailed review of recent advances in delivery vectors for use in techniques such as gene augmentation, with particular emphasis on useful applications of antisense and ribozyme technology.