A network of pattern recognition receptors (PRRs) is responsible for the detection of invading viruses and acts as the trigger for the host antiviral response. Central to this apparatus is stimulator of interferon genes (STING), which functions as a node and integrator of detection signals. Owing to its role in both intrinsic and adaptive immunity, STING has become a focus for researchers in the field of oncolytic virotherapy. In this review, we consider the function of the cGAS-STING axis and its regulation, both by cellular mechanisms and as a result of viral interference.