The mammalian cyclic dinucleotide 2', 3'-cGAMP is a potent inducer of innate immune responses produced upon detection of cytosolic DNA by cGAS. The mechanisms underlying the control of intracellular cGAMP levels remained unclear. In a new study, Eaglesham et al. identified poxins as 2', 3'-cGAMP-specific nucleases allowing immune evasion by viruses.