The study of bacterial stress response systems is an important area of research with wide-ranging implications, from understanding the basic bacterial physiology to developing new antimicrobial treatments. This dissertation presents my recent efforts to understand how Gram-negative bacteria adapt to environmental stimuli using live cell fluorescence imaging, genetic engineering, bulk biochemical/cellular assays, and microfluidic mechanical manipulations. Employing these methods, I, in collaboration with others, investigated three types of stress response systems associated with the Gram-negative bacteria cell envelope: multidrug efflux pumps (MEPs), two-components signal transduction systems (TCSs), and metal homeostasis.