Cyclic dinucleotides are employed in all domains of life as second messengers for diverse functions. It has been recently appreciated that these signaling molecules have conserved roles as part of immune surveillance systems to detect infections. Cyclic dimeric adenosine monophosphate (c-di-AMP) is produced by bacteria and archaea but not by mammalian cells. Bacteria employ this dinucleotide to adapt to various stress conditions and for virulence in pathogens, serving as a crucial molecule for physiology and pathogenesis. Intracellular homeostasis in bacteria is achieved by regulation of diadenylate cyclases that make c-di-AMP, phosphodiesterases that degrade it, and secretion mechanisms. In the host cells, c-di-AMP is detected as a pathogen-associated molecular pattern (PAMP) by several innate immune system proteins, including STING, DDX41, RECON, and ERAdP, to affect proinflammatory cytokine production. Additionally, it has also been shown that c-di-AMP activates the NLRP3 inflammasome in a STING-independent pathway, which leads to IL-1β production. Overall, these findings indicate that c-di-AMP produced by bacterial pathogens plays an important role in mammalian host inflammatory responses during infection.