The life of any organism depends on the ability of cells to accurately recognize and eliminate harmful microbes. In order to detect the immense repertoire of pathogenic entities, the innate immune system of mammals has evolved distinct sensing strategy, a major one of which is based on the recognition of DNA - the basic building blocks of “life” itself. Integral to this process are intracellular DNA-binding proteins that, upon interaction with DNA, initiate tightly regulated signalling cascades that trigger a series of cellular events, which ultimately promote an inflammatory response. While this process was originally discovered as crucial component of innate immune defence against pathogens, recent work has elucidated a role for cytosolic DNA recognition pathways beyond the traditional realm of innate immunity. In this talk an update of our current progress on innate DNA sensing and signalling will be presented.