Innate immunity, our inborn immediate defence mechanism, was thought for a long time to be non-specific and, consequently, research into innate mechanisms often took second place to research into adaptive immunity. In recent decades, however, the spotlight has shone on groundbreaking advances into mechanisms of innate immunity; from the hypothesis that mitogen receptors distinguish between ‘self’ and ‘very-different-from-self’ in the mid-1970s to the refining of the concept by Janeway in 1989, the identification of Toll-like molecules as mitogen receptors, and finally the cloning of the first mammalian Toll-like receptor (TLR) in 1997. We now know that innate immune activation has a role in the control of adaptive immune responses, and many more TLRs and their ligands have been characterised.