Toll-like receptors (TLRs) are the archetypal pattern recognition receptors (PRRs) envisioned by Janeway (1989) as innate sensors of pathogen attack and host triggers of an adaptive immune response. Two recent papers (Choe et al., 2005, Bell et al., 2005) reveal the distinctive architecture of a TLR sensor domain and hint at how this structural design facilitates the recognition of a wide array of pathogen molecules.