Transcriptional activation in bacteria usually involves an activator protein that binds to sites near the target promoter. Some activators of sigma(54)-RNA polymerase holoenzyme, however, can stimulate transcription even when their DNA-binding domains are removed. Recent studies have revealed examples of sigma(54)-dependent activators that naturally lack DNA-binding domains and seem to activate transcription from solution rather than from specific DNA sites. In addition, some activators that function with other forms of RNA polymerase holoenzyme, including Bacillus subtilis Spx and the bacteriophage N4 single-stranded DNA-binding protein, also stimulate transcription without binding to DNA. Because binding to regulatory sites enables activators to stimulate transcription from specific promoters, alternative strategies for achieving specificity are required for activators that do not bind to DNA.