Chronic inflammation generates damage-associated molecular patterns (DAMPs) such as DNA that impact immune responses. DNA is sensed to activate the Stimulator of Interferon Genes (STING) adaptor which may stimulate or suppress immunity. In some cancer models DNA suppresses anti-tumour immunity to promote tumour growth by inducing indoleamine 2,3 dioxygenase (IDO). STING agonists enhance anti-tumour immunity but fail to control tumour growth unless immune checkpoints are also disrupted. DNA sensing pathways can also be exploited to attenuate autoimmunity in several models of clinical autoimmune syndromes. Hence, STING agonists can be used to manipulate immune balance in a range of chronic conditions.