Expression of the genome is primarily regulated at the level of transcription by gene-specific transcription factors, which recognize specific DNA sequences to activate or inhibit transcription. The ability to control gene expression at will would provide scientists with a powerful tool for biotechnology and drug-discovery research. Over the last decade or so, researchers have made great strides in our understanding of the structures and mechanisms of action of naturally occurring transcription factors. Such research has revealed that members of the Cys2-His2 zinc finger family of transcription factors consist of functional modules that recognize a wide variety of DNA sequences. This review describes recent advances in the development of novel methods to design and construct artificial transcription factors to control gene expression at will. The applications of artificial transcription factors in the areas of medicine and biotechnology are discussed.