A critical factor for bacterial survival in any environment is the ability to sense and respond appropriately to insults that cause stress to the cell, threatening its survival. Most of these stressors first affect the outer surface of the bacterial cell, are sensed in some way, and defense measures are enacted in response. If the bacteria successfully respond to an encountered stress, they survive and multiply. If they are unsuccessful or inefficient in their response, it can result in death. Efficiently responding to factors that induce stress is especially important for bacteria that inhabit environments that are constantly changing, or for those that inhabit more than one biological niche. In addition, bacterial species that associate with humans and other organisms must be able to overcome stresses that are produced by the host immune response in order to colonize and cause disease. The wide variety of stressors encountered by bacteria has resulted in countless strategies that are used by pathogens to overcome these insults, which we continue to identify. Clearly, a better understanding of these stress response mechanisms may be useful for developing new strategies to combat bacteria that cause certain infectious diseases. This Research Topic aims to highlight our increasing understanding of mechanisms by which bacteria sense and respond to stresses encountered in the host or other environments. Examples of stress response mechanisms of interest include, but are not limited to those that respond to antimicrobials, host immune responses, or environmental changes.