Aberrant gene expression is a fundamental cause of many disease-associated pathophysiologies. The pharmacological modulation of transcription factor activity therefore represents an attractive therapeutic approach to such disorders. With the exception of nuclear receptors, which are the direct targets of pharmaceuticals, other known classes of transcription factors are largely regulated indirectly by drugs that impact upon those signal transduction cascades that alter transcription factor phosphorylation and dephosphorylation and/or nuclear import. However, recent advances in drug discovery technologies now enable high-throughput screens that can identify molecules that act directly at the level of transcription factor complexes.