The RpoS-mediated general stress response in *Escherichia coli* is a key mechanism for stress resistance. RpoS, a sigma factor, is induced under stress or nutrient deprivation, leading to the expression of genes that help the cell survive. During exponential growth, RpoS is low and rapidly degraded, but under stress, its levels increase. The induction of RpoS involves multiple levels of regulation, including transcription, translation, and degradation. Stress conditions trigger specific small RNAs (sRNAs) that stimulate RpoS translation, and the response is regulated by factors like Hfq, (p)ppGpp, and RssB. RpoS-dependent genes help the cell resist various stresses, including low pH, high temperature, and osmotic shock. The RpoS response is distinct from specific stress responses, as it provides cross-protection against multiple stresses. RpoS interacts with the core RNA polymerase to regulate gene expression, and its activity is controlled by various regulatory cascades, including the stringent response and the PhoPQ system. The RpoS regulon includes genes involved in stress resistance, biofilm formation, and osmoprotection. The regulation of RpoS involves complex interactions between sRNAs, antiadaptors, and other regulatory proteins, ensuring proper induction and degradation of RpoS under different conditions. The RpoS response is essential for survival under stress and plays a critical role in bacterial adaptation to changing environments.The RpoS-mediated general stress response in *Escherichia coli* is a key mechanism for stress resistance. RpoS, a sigma factor, is induced under stress or nutrient deprivation, leading to the expression of genes that help the cell survive. During exponential growth, RpoS is low and rapidly degraded, but under stress, its levels increase. The induction of RpoS involves multiple levels of regulation, including transcription, translation, and degradation. Stress conditions trigger specific small RNAs (sRNAs) that stimulate RpoS translation, and the response is regulated by factors like Hfq, (p)ppGpp, and RssB. RpoS-dependent genes help the cell resist various stresses, including low pH, high temperature, and osmotic shock. The RpoS response is distinct from specific stress responses, as it provides cross-protection against multiple stresses. RpoS interacts with the core RNA polymerase to regulate gene expression, and its activity is controlled by various regulatory cascades, including the stringent response and the PhoPQ system. The RpoS regulon includes genes involved in stress resistance, biofilm formation, and osmoprotection. The regulation of RpoS involves complex interactions between sRNAs, antiadaptors, and other regulatory proteins, ensuring proper induction and degradation of RpoS under different conditions. The RpoS response is essential for survival under stress and plays a critical role in bacterial adaptation to changing environments.