NF-κBs are a family of transcription factors that control a number of essential cellular functions including immune responses, cell proliferation and antiapoptosis. NF-κB activities are tightly regulated through upstream signaling molecules and downstream feedback loops. In this review, structural discoveries in the NF-κB pathway are presented. With the structure information, the following questions may be addressed: (1) How do NF-κBs activate their target genes? (2) How do IκBs inhibit NF-κB activities in the steady state? (3) How do upstream signaling molecules activate the NF-κB pathway? and (4) How do the feedback loops shut down the NF-κB pathway to avoid constitutive NF-κB activation?