All organisms require the ability to respond appropriately to changes in their environment. Inhabiting diverse environments from dry deserts to deep-sea hydrothermal vents with only membrane layers separating their cytoplasm from the external world, bacteria are constantly interacting with their environment and being challenged by them to evolve. They adapt exceptionally quickly to these transitions via complex genetic, transcriptional, and post-transcriptional mechanisms (4β16). Studying the regulated and stochastic responses of bacteria to environmental pressures is significant to the advancement of our understanding of biological adaptation as well as the improvement of therapeutics for human health. In this dissertation, I discuss how two enteric model organisms adapt genetically to host-associated selective pressures and how the findings of these studies provide fundamental insights into microbial adaptation that can be used to improve clinical therapies for humans