Activation of the NF-xcexbaB transcription factor and its associated gene expression in microglia is a key component in the response to brain injury. Its activation is dynamic and is part of a network of biochemical species with multiple feedback regulatory mechanisms. Mathematical modeling, which has been instrumental for understanding the NF-xcexbaB response in other cell types, offers a valuable tool to investigate the regulation of NF-xcexbaB activation in microglia at a systems level.