Different types of second messenger molecules play important roles in bacterial physiological activities. 3", 5"-cyclic adenosine monophosphate (cAMP), as a second messenger of nucleotides, is widely present in bacteria. Under normal physiological conditions, there is a dynamic balance between the synthesis and metabolism of cAMP in bacterial cells, and it functions through complexes formed with its receptor proteins Crp master transcription regulator. This article reviews the pressure stress regulatory mechanisms of cAMP-Crp in lethal stress, bacterial population competition, and biofilm formation, as well as the pathways through which cAMP affects virulence in different pathogens. It calls for researchers to pay attention to the upstream pathways of bacterial cAMP in response to host or external environmental changes. A comprehensive understanding of cAMP-mediated bacterial stress and virulence regulation may contribute to better prevention and treatment of bacterial infections.