Transcription factors play an important role in the long-term regulation of cell growth, differentiation and responses to environmental cues. There is growing evidence that these proteins are closely associated with control at the genetic level of the development and maintenance of the diseased state, and might therefore provide selective targets for novel pharmaceutical intervention. The vast array of information available on the three-dimensional structure of transcription factors and the intricate molecular machineries that fine-tune their activity offer opportunities for embarking on the rational design of drugs directed against specific transcription factors, thus producing potent new agents that modulate their function in a plethora of clinically important situations.