The article by Battesti, Majdalani, and Gottesman reviews the RpoS-mediated general stress response in *Escherichia coli*. Under conditions of nutrient deprivation or stress, *E. coli* and related bacteria increase the accumulation of RpoS, a specialized sigma factor, which leads to general stress resistance. During rapid growth, RpoS translation is inhibited, and any synthesized RpoS protein is rapidly degraded. The transition from exponential growth to stationary phase has been partially dissected by analyzing RpoS induction after specific stress treatments. Different stress conditions lead to the induction of specific sRNAs that stimulate RpoS translation or induce specific genes that help the cell deal with the stress. The RpoS response is characterized by rapid induction of RpoS levels, regulation at multiple levels (transcription, translation, degradation, and activity), and a wide range of stresses affecting RpoS accumulation. The RpoS regulon includes genes that are RpoS-specific and those also expressed by the vegetative sigma factor, RpoD, under certain conditions. The review discusses the signaling cascades leading to RpoS induction, the outcome of RpoS induction, and the recovery process. Key regulatory mechanisms include the stringent response, which uses (p)ppGpp as a signaling molecule, and the role of small RNAs (sRNAs) in regulating RpoS translation. The ClpXP ATP-dependent protease degrades RpoS, and the adaptor protein RssB is crucial for this process. The activity of RpoS is regulated by factors such as Crl, Rsd, and 6S RNA, which help RpoS compete for core RNA polymerase. The article also reviews the regulatory cascades for specific stress responses, such as the starvation response driven by (p)ppGpp, and the role of sRNAs in specific stress responses like low temperature, high osmolarity, and acid stress. The induction of RpoS by these stresses involves specific pathways and the activation of genes that provide protection from the stress. Overall, the RpoS-mediated general stress response in *E. coli* is a complex and multifaceted process that involves multiple regulatory mechanisms and genes, providing the cell with a broad range of stress resistance mechanisms.The article by Battesti, Majdalani, and Gottesman reviews the RpoS-mediated general stress response in *Escherichia coli*. Under conditions of nutrient deprivation or stress, *E. coli* and related bacteria increase the accumulation of RpoS, a specialized sigma factor, which leads to general stress resistance. During rapid growth, RpoS translation is inhibited, and any synthesized RpoS protein is rapidly degraded. The transition from exponential growth to stationary phase has been partially dissected by analyzing RpoS induction after specific stress treatments. Different stress conditions lead to the induction of specific sRNAs that stimulate RpoS translation or induce specific genes that help the cell deal with the stress. The RpoS response is characterized by rapid induction of RpoS levels, regulation at multiple levels (transcription, translation, degradation, and activity), and a wide range of stresses affecting RpoS accumulation. The RpoS regulon includes genes that are RpoS-specific and those also expressed by the vegetative sigma factor, RpoD, under certain conditions. The review discusses the signaling cascades leading to RpoS induction, the outcome of RpoS induction, and the recovery process. Key regulatory mechanisms include the stringent response, which uses (p)ppGpp as a signaling molecule, and the role of small RNAs (sRNAs) in regulating RpoS translation. The ClpXP ATP-dependent protease degrades RpoS, and the adaptor protein RssB is crucial for this process. The activity of RpoS is regulated by factors such as Crl, Rsd, and 6S RNA, which help RpoS compete for core RNA polymerase. The article also reviews the regulatory cascades for specific stress responses, such as the starvation response driven by (p)ppGpp, and the role of sRNAs in specific stress responses like low temperature, high osmolarity, and acid stress. The induction of RpoS by these stresses involves specific pathways and the activation of genes that provide protection from the stress. Overall, the RpoS-mediated general stress response in *E. coli* is a complex and multifaceted process that involves multiple regulatory mechanisms and genes, providing the cell with a broad range of stress resistance mechanisms.