T he innate immune system provides an important first line of defense against invading pathogens or harmful damages. Over the past decade, our understanding on the recognition of pathogenic nucleic acids by innate immunity has advanced considerably by the discovery of the DNA-sensing receptor cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) synthase (cGAS) and its downstream effector stimulator of interferon genes (STING). The cGAS–STING signaling pathway is activated by various DNA microbes, leading to increased cytokine production and upregulation of type I interferon (IFN) gene expression. Subsequent studies reveal that the cGAS–STING signaling pathway is also activated by host DNAs such as mitochondrial and nuclear DNAs aberrantly localized in the cytosol, which has become an important mechanism triggering chronic inflammatory diseases, e.g. type 2 diabetes, non-alcoholic fatty liver diseases, and kidney diseases. To help researchers better understand the mechanisms regulating cGAS/STING activities and the roles of the cGAS–STING signaling pathway in various immune- and non-immune-related biological events, Journal of Molecular Cell Biology is pleased to present a collection entitled ‘cGAS–STING signaling in health and diseases’ that reviews recent advances in the field.