Gene repair provides a number of obvious advantages over traditional gene therapy using viral vectors and transgene expression. Although common pathways and factors may exist between the different DNA correction strategies, it will be important to know the precise mechanisms before we begin to use gene repair for the treatment of genetic diseases. Once the critical rate-limiting factors/pathways are identified, we may be able to manipulate them and increase the frequencies of correction. For this purpose, the liver may provide an ideal target organ for the isolation and characterization of the relevant molecules, as well as their potential manipulation via different agents. The delivery of nucleic acids is critical to each of the different approaches, and more efficient systems must be developed for both cells and their nuclei. Radical changes in the basic oligonucleotide backbone may provide greater affinity of binding as well as increased nuclease resistance. Virasomes combine the advantages of nonviral and viral delivery and may be used to improve transfection efficiency to the rat liver via the biliary tract. Transmembrane peptides such as penetratin may provide a mechanism to avoid the harsh environment of the endosome and more efficiently translocate to the nucleus. The genetic repair observed using 40 to 45 mer SSOs simply confirms what was reported more than 10 years ago; however, with more efficient delivery systems, we have significantly improved the conversion rates. An SSO is a simple-structured molecule that is inexpensive to manufacture and relatively easy to synthesize. Instead of creating more complex molecular systems, perhaps we should recognize and take advantage of the cell's inate ability to rewrite the sequence of its own DNA. By recognizing the importance of delivery and the rules of mass action, the science of gene therapy may now become the art of gene repair. The ideal repair molecule might be a synthetic molecule consisting of a nuclease-resistant backbone, a targeting ligand, an endosomal disrupter, and a nuclear localizing peptide. Although a generic design of the molecule is feasible, targeting it to the precise nucleotide defect will be based on an individual's genetic sequence. As the 20th century witnessed the creation of "designer jeans," the 21st century is beginning to observe the development of "designer gene therapy." The potential application of these strategies to clinical medicine is vast and includes targeted genetic repair, functional genomics, and pharmacogenetics. The prospect of being able to simply correct a gene defect provides a major shift in the paradigm of clinical and basic science that, hopefully, will be realized in the coming years.