The transcription factor NF-kappaB is known for its function in regulating immune and inflammatory responses. However, recent evidence suggests that NF-kappaB also plays a pivotal role in controlling cell proliferation, apoptosis, and cell migration. Deregulated activation of NF-kappaB has been observed in various cancers. Over the past few years. significant progress has been made to elucidate the mechanisms of NF-kappaB activation in both normal and cancer cells. Notably, a large number of protein kinases have been shown to stimulate NF-kappaB activity under different conditions, and some of these kinases are aberrantly activated in cancer cells. In this review, we discuss our current knowledge of NF-kappaB activation, with a focus on the NF-kappaB-activating kinases and their roles in cancer formation.