The design and selection of DNA-binding proteins or individual domains capable of novel sequence recognition continues to make great strides. Recent studies have also highlighted the role of the non-DNA-contacting portions of the protein and the optimal assembly of the domains. For the first time, it appears that it is possible to produce proteins capable of targeting any gene with an 18 base pair recognition domain. A variety of applications are being explored, such as targeted transcriptional regulation, recombination and viral integration. These proteins will probably find diverse applications in gene therapy, functional genomics, and agriculture.