Members of the NF-kappaB family of transcription factors play critical roles in regulating immunity and cell survival and contribute to cancer progression and chemoresistance. Over the past 20 years, much has been learned about the remarkable complexity in regulation of NF-kappaB signaling. In particular, recent studies have added to our current understanding of the roles of a multitude of posttranslational modifications in this signaling system: these include phosphorylation, acetylation, nitrosylation, ubiquitination, neddylation and sumoylation. This review will highlight our current knowledge of the roles of sumoylation in regulating NF-kappaB signaling and functions and will address future perspectives.