The general stress response (GSR) is a widespread strategy in bacteria to adapt to changing environments. The GSR is activated by various stresses and leads to a global response that protects cells against multiple stressors. In *E. coli*, the alternative sigma factor RpoS is the central regulator of the GSR and is conserved in most γ-proteobacteria. RpoS is induced under nutrient deprivation and other stresses, primarily through activation of RpoS translation and inhibition of proteolysis. This review summarizes recent advances in understanding how stresses lead to RpoS induction and the identification of RpoS-dependent genes and pathways. RpoS is a key regulator of the GSR, involved in various stress responses, including oxidative stress, acid resistance, and osmotic stress. It is regulated by multiple factors, including transcriptional and translational regulators, as well as post-translational modifications. The regulation of RpoS involves complex interactions between various proteins, including ArcA, Crp/cAMP, MqsA, and GadX, which can either activate or repress RpoS expression. Additionally, small regulatory RNAs (sRNAs) play a crucial role in regulating RpoS translation by interacting with the 5' UTR of the rpoS mRNA. The regulation of RpoS is also influenced by the stability of the RpoS protein, which is controlled by proteolytic systems such as RssB and ClpXP. RssB binds to RpoS and delivers it to ClpXP for degradation, while Ira anti-adaptors inhibit RssB activity, stabilizing RpoS. These regulatory mechanisms allow bacteria to switch between growth and survival modes in response to environmental changes. The GSR is essential for bacterial survival, as it enables cells to adapt to various stress conditions. However, the balance between growth and survival is a trade-off, as high RpoS levels can be detrimental to growth. Understanding the regulation of RpoS and its role in the GSR is crucial for elucidating the mechanisms by which bacteria respond to environmental challenges. The study of RpoS and its regulatory networks provides insights into the complex interplay between stress responses and metabolic adaptations in bacteria.The general stress response (GSR) is a widespread strategy in bacteria to adapt to changing environments. The GSR is activated by various stresses and leads to a global response that protects cells against multiple stressors. In *E. coli*, the alternative sigma factor RpoS is the central regulator of the GSR and is conserved in most γ-proteobacteria. RpoS is induced under nutrient deprivation and other stresses, primarily through activation of RpoS translation and inhibition of proteolysis. This review summarizes recent advances in understanding how stresses lead to RpoS induction and the identification of RpoS-dependent genes and pathways. RpoS is a key regulator of the GSR, involved in various stress responses, including oxidative stress, acid resistance, and osmotic stress. It is regulated by multiple factors, including transcriptional and translational regulators, as well as post-translational modifications. The regulation of RpoS involves complex interactions between various proteins, including ArcA, Crp/cAMP, MqsA, and GadX, which can either activate or repress RpoS expression. Additionally, small regulatory RNAs (sRNAs) play a crucial role in regulating RpoS translation by interacting with the 5' UTR of the rpoS mRNA. The regulation of RpoS is also influenced by the stability of the RpoS protein, which is controlled by proteolytic systems such as RssB and ClpXP. RssB binds to RpoS and delivers it to ClpXP for degradation, while Ira anti-adaptors inhibit RssB activity, stabilizing RpoS. These regulatory mechanisms allow bacteria to switch between growth and survival modes in response to environmental changes. The GSR is essential for bacterial survival, as it enables cells to adapt to various stress conditions. However, the balance between growth and survival is a trade-off, as high RpoS levels can be detrimental to growth. Understanding the regulation of RpoS and its role in the GSR is crucial for elucidating the mechanisms by which bacteria respond to environmental challenges. The study of RpoS and its regulatory networks provides insights into the complex interplay between stress responses and metabolic adaptations in bacteria.