AbstractGas molecules are ubiquitous in the environment and are used as nutrient and energy sources for living organisms. Many organisms, therefore, have developed gas‐sensing systems to respond efficiently to changes in the atmospheric environment. In microorganisms and plants, two‐component systems (TCSs) and transcription factors (TFs) are two primary mechanisms to sense gas molecules. In this review, gas‐sensing transcriptional regulators, TCSs, and TFs, focusing on protein structures, mechanisms of gas molecule interaction, DNA binding regions of transcriptional regulators, signal transduction mechanisms, and gene expression regulation are discussed. At first, transcriptional regulators that directly sense gas molecules with the help of a prosthetic group is described and then gas‐sensing systems that indirectly recognize the presence of gas molecules is explained. Overall, this review provides a comprehensive understanding of gas‐sensing transcriptional regulators in microorganisms and plants, and proposes a future perspective on the use of gas‐sensing transcriptional regulators.