This review deals with the transcriptional regulation of heat shock or stress genes that are present in every organism studied to date. While some of these genes are expressed constitutively and appear to be involved in basic cellular processes such as protein synthesis and maturation, assembly of protein complexes, and intracellular trafficking, others are normally silent or are expressed at low levels. Expression of the latter genes is enhanced when cells are subjected to stressful conditions such as elevated temperature and other physical and chemical insults or at specific stages of organismal development. The upregulation of these genes correlates with the development of tolerance to subsequent, similar insults. Upregulation following environmental insults appears to be mediated by heat shock transcription factor. This article summarizes what is known about the promoters of regulated stress genes in higher eukaryotes and the mechanisms by which heat shock transcription factor or developmental regulators control their activation. Recent data pointing to a possible connection between the activation of stress genes and general signal transduction pathways are also discussed, as they suggest an integration of the stress response and other cellular control mechanisms.