Recent studies have clearly linked nuclear factor-kappaB (NF-κB), a transcription factor that plays a central role in regulating immune and inflammatory responses, to tumor development, progression, and metastasis as well as tumor therapy resistance. However, it still remains largely unknown on how the tightly regulated NF-κB becomes constitutively activated in tumorigenesis and how the original cancer immunosurveillance function of NF-κB is transformed to be tumorigenic. To address these important issues for cancer prevention and treatment, we discuss current understanding of the molecular mechanisms and molecules involved in the oncogenic activation of NF-κB. We also discuss current understanding of how NF-κB coordinates the inflammatory and malignant cells in tumorigenesis.