cGAS is a conserved immune sensor in eukaryotes that detects cytosolic DNA and activates innate immune responses. It plays a critical role in human immunity by sensing double-stranded DNA (dsDNA) and producing cyclic dinucleotides (CDNs), which activate the STING pathway to induce anti-microbial and inflammatory responses. cGAS is also found in bacteria, where it functions in anti-phage defense systems called CBASS. These systems detect phage infection and trigger cell death to prevent viral replication. cGAS-like proteins in bacteria produce various CDN second messengers, including 3'3'-cGAMP and 2'3'-cGAMP, which activate STING and other effectors. Bacterial cGAS is activated by various ligands, including nucleic acids, and can be regulated by accessory proteins that modulate its activity. The cGAS-STING pathway is conserved across species, with variations in the specific CDNs produced and the mechanisms of activation. Phages have evolved strategies to counteract cGAS-like signaling, including nucleases that degrade CDN second messengers and proteins that sequester them. Understanding cGAS and its homologs in bacteria provides insights into the evolution of immune defense mechanisms and may lead to new therapeutic strategies for infectious diseases.cGAS is a conserved immune sensor in eukaryotes that detects cytosolic DNA and activates innate immune responses. It plays a critical role in human immunity by sensing double-stranded DNA (dsDNA) and producing cyclic dinucleotides (CDNs), which activate the STING pathway to induce anti-microbial and inflammatory responses. cGAS is also found in bacteria, where it functions in anti-phage defense systems called CBASS. These systems detect phage infection and trigger cell death to prevent viral replication. cGAS-like proteins in bacteria produce various CDN second messengers, including 3'3'-cGAMP and 2'3'-cGAMP, which activate STING and other effectors. Bacterial cGAS is activated by various ligands, including nucleic acids, and can be regulated by accessory proteins that modulate its activity. The cGAS-STING pathway is conserved across species, with variations in the specific CDNs produced and the mechanisms of activation. Phages have evolved strategies to counteract cGAS-like signaling, including nucleases that degrade CDN second messengers and proteins that sequester them. Understanding cGAS and its homologs in bacteria provides insights into the evolution of immune defense mechanisms and may lead to new therapeutic strategies for infectious diseases.