Based on an evolutionary conserved repertoire Toll-like-receptors (TLRs) donate specificity to innate immune cells. Therefore, TLRs are considered as paradigmatic for "self" versus "non-self" discrimination. This view, however, needs to be modified since TLR's also appear to recognise "endogeneous", that is host-derived ligands, examples being host-derived DNA and -RNA. Here I discuss physiological and pathophysiological consequences of endogeneous ligand-recognition by TLRs. I conclude that endogeneous ligand recognition by TLRs drives sterile inflammation sustained by innate immune cells in certain autoimmune disorders.