Cyclic diadenosine monophosphate (c-di-AMP) is a ubiquitous class of second messenger molecule in bacteria, whose metabolism is finely tuned by diadenylate cyclase (DAC) and phosphodiesterase (PDE). c-di-AMP is not only involved in many essential processes such as cell growth, cell wall homeostasis and ion transport, but also in host anti-bacterial immunity through being sensed by eukaryotic sensors/receptors of host cells. In particular, c-di-AMP has been found to play important roles in regulating host innate immunity such as type I interferon response, activation of NF-κB signal pathway, autophagy and inflammatory response. Acting as a mucosal adjuvant, c-di-AMP induces host adaptive immune response as well. Thus c-di-AMP is now considered to be a newly identified pathogen associated molecular pattern (PAMP), which becomes a new target in bacterial vaccines and drug research.