Transcription by RNA polymerase utilizing the alternative sigma factor sigma(54) is regulated by a distinct class of positive activators designated the sigma(54)-dependent family. The activities of these regulators are themselves modulated in response to a wide variety of environmental signals. Factors that modulate the expression or the activity of the regulatory protein in response to chemical and metabolic changes are ultimately responsible for determining the level of expression of sigma(54)-dependent genes and hence the diverse bacterial functions that they encode. Many members of the sigma(54)-dependent family are part of two-component sensor-response systems. This MicroReview emphasizes recent data concerning the activities of a distinct subgroup of the sigma(54)-dependent regulators that directly sense and respond with transcriptional activation to the presence of small effector molecules in their environment. The functional consequences of effector activation in terms of regulation of the enzymatic (ATPase) activity of these transcriptional activators and interdomain interactions are discussed.