(1) Different types of DNAs are presented, ordered according to the predicted sensitivity of cGAS to these molecules 1, 3, 8 (note: a concurrent analysis of these DNA forms has not been performed to date). Short dsDNAs are ~45–70 bp long 1, with the 45‐bp ISD (interferon stimulatory DNA) being the prototypical sequence used as cGAS ligand (although not representing a physiological DNA produced by the cell). (2) Endogenous nucleases limit the cytoplasmic accumulation of DNAs from (1) (note: the type of endogenous DNA processed by SAMHD1 is unknown) 2, 6, 9, 10. (3) Cytoplasmic DNAs bypassing nuclease degradation bind and activate cGAS. Long dsDNAs (e.g. bacterial genomic DNA) may better avoid nuclease degradation, which may enhance further the sensitivity of cGAS for these DNAs. The combination of cGAS affinity together with resistance to nuclease degradation controls self‐ and non‐self‐cytoplasmic DNA sensing by cGAS.