The current non-viral approaches to gene therapy are presented with a particular emphasis on receptor-mediated DNA delivery and the recent advances made that make this approach an attractive alternative to viral-based vector systems. The general strategy for receptor-mediated DNA delivery involves condensing DNA via electrostatic interaction with a polycation, e.g. polylysine, chemically linked to a cell binding ligand, e.g. transferrin. The potency of this delivery system has recently been improved by incorporating an endosome disrupting (endosomolytic) agent into the DNA-complex, such as adenovirus particles, which enhances release into the cytoplasm. Therefore, the approach now is to mimic viral entry mechanisms, e.g. by incorporating a synthetic peptide with endosomolytic activity, and, in effect, manufacture a synthetic virus.