The eukaryotic transcription factor NF-κB regulates a wide range of host genes that control the inflammatory and immune responses, programmed cell death, cell proliferation and differentiation. The activation of NF-κB is tightly controlled both in the cytoplasm and in the nucleus. While the upstream cytoplasmic regulatory events for the activation of NF-κB are well studied, much less is known about the nuclear regulation of NF-κB. Emerging evidence suggests that NF-κB undergoes a variety of posttranslational modifications, and that these modifications play a key role in determining the duration and strength of NF-κB nuclear activity as well as its transcriptional output. Here we summarize the recent advances in our understanding of the posttranslational modifications of NF-κB, the interplay between the various modifications, and the physiological relevance of these modifications.