Bacteria, irrespective of natural habitat, are exposed to constant fluctuations in their growth conditions. Consequently they have developed sophisticated responses, modulated by the re-modelling of protein complexes and by phosphorylation-dependent signal transduction systems, to adapt to and to survive a variety of insults. Ultimately these signalling systems affect transcriptional regulons either by activating an alternative sigma factor subunit of RNA polymerase, for example, sigma E (sigma(E)) of Escherichia coli and sigma B (sigma(B)) and sigma F (sigma(F)) in Bacillus subtilis or by activating DNA-binding two-component response regulators. Recent structure determinations, and systems biology analysis of key regulators in well-characterised stress-responsive pathways, illustrate conserved and novel mechanisms in these representative model bacteria.