Drug-delivery systems based on lipid-DNA complexes. Drug delivery with plasmid DNA is a promising strategy for the treatment of many conditions, including cancer. With appropriate materials and formulations, it is possible to achieve good in vitro transfection efficiency of plasmid DNA, but the in vivo delivery is generally very inefficient, requiring administration of high doses to obtain therapeutic benefit. Several different strategies have been used to enhance the delivery of plasmid DNA, including modification of the plasmid by addition of chemical moieties, co-administration of proteins, use of carriers such as polymers and liposomes, and administration in conjunction with other techniques such as electroporation. In this paper, recent research on lipid-DNA formulations is reviewed, with particular emphasis on the use of this approach for efficient gene delivery and nucleic acid therapy. The progress made towards translating these lipid-DNA formulations into clinical applications is discussed, including formulations with both positively and negatively charged lipid-DNA complexes, which are currently being investigated in ongoing clinical trials. It is concluded that transfection efficiency of plasmid DNA in cell culture can be improved greatly by formulation with a variety of lipids. However, more in vivo research is required to establish the therapeutic usefulness of lipid-DNA formulations, and this is likely to be greatly facilitated by the use of novel, highly sensitive non-invasive imaging technology.