Dendritic cells (DCs) produce an array of cytokines after detecting various immune adjuvants through pattern recognition receptors (PRRs). PRR signaling leads to activation of transcription factors such as NF-kappaB or interferon regulatory factors (IRFs) but after activation must be attenuated to avoid immunopathology and to maintain tissue homeostasis. IkappaB kinase family members, originally identified as classical NF-kappaB activators, are now found to be broadly and crucially involved in PRR signaling in a member-specific manner. Furthermore, a new mechanism for NF-kappaB downregulation is emerging that involves the degradation of active NF-kappaB by the nuclear ubiquitin-proteasome system. Here we review new aspects of NF-kappaB and IRF regulation chiefly in DCs.