Immune responses demand not only rapid activation but also appropriate termination of signaling/transcriptional effectors. In fact, immune response signaling is highly dynamic and stimulus/pathogen-specific. Thus it is not surprising that an increasing number of negative feedback regulators are being identified, but it is often unclear whether they have overlapping function (representing fail-safe mechanisms) or specific functions. I will present my laboratorys combined kinetic modeling and experimental work to distinguish the functions of negative feedback regulators and show that their kinetic properties are key to understanding their physiological functions.