Toll-like receptors (TLRs) recognize pathogen-associated products, such as components of the bacterial cell wall, and activate macrophages and other innate immune cells through a signaling cascade involving serine/threonine kinases of the IRAK family. Richard Flavell and co-workers from Yale University School of Medicine, New Haven, Connecticut report in 26 July Cell that at least one member of the IRAK family, IRAK-M, is a negative regulator of TLR signaling (Cell 2002, 110:191-202). They suggest IRAK-M controls a balance between the innate immune response and excessive production of cytokines, which can be potentially harmful to the host.