Here we discuss compartment-specific characteristics of STING expression and signaling in the TME; recent evidence for STING pathway suppression in the CNS; efforts to target STING therapeutically in cancer clinical trials; and potential future implications of STING modulation for the efficacy of virotherapy, standard-of-care chemo/radiation, and other modalities being investigated for targeting CNS tumors (Figure 1B). The gene discussed is STING1; the disease is cancer.