The ability to adapt to diverse stresses is critical for the survival of bacteria in the environment. Here we address how Enterobacteriaceae adapt to dehydration and polymyxins. Dehydration is an environmental stress that many bacteria encounter in their ecological niches. However, the mechanisms involved in surviving dehydration are not well understood, particularly in Gram-negative bacteria. In Chapter 2 we develop a dehydration assay and conduct genetic screens to identify genes important for dehydration survival in Escherichia coli. We identify several key regulators that contribute to dehydration survival, including the transcriptional regulator DksA and the general stress response regulator RpoS. In addition to studying dehydration tolerance, we investigate resistance to polymyxins, which are cationic antimicrobial peptides used as last-resort antibiotics in Gram-negative bacteria. The polymyxin resistance network differs in network topology, which refers to how the regulators are connected to and interact with each other, across several genera of Enterobacteriaceae. These differences shape how this network can be activated and influence the types of mutations that give rise to spontaneous polymyxin resistance. In Chapter 3, we determine how network topology affects the relative importance of different regulators in polymyxin resistance and show how environmental conditions modulate the activity of a connector protein in this network. Taken together, these studies contribute to our understanding of how bacteria sense and respond to environmental stressors.