Atherosclerosis is a chronic inflammatory disease of the arterial wall with lipid-laden lesions, involving a complex interaction between multiple different cell types and cytokine networks. Inflammatory responses mark all stages of atherogenesis: from lipid accumulation in the intima to plaque formation and eventual rupture. One of the most important regulators of inflammation is the transcription factor nuclear factor-κB (NF-κB), which is activated through the canonical and noncanonical pathways in response to various stimuli. NF-κB has long been regarded as a proatherogenic factor, because it is implicated in multiple pathological processes during atherogenesis, including foam cell formation, vascular inflammation, proliferation of vascular smooth muscle cells, arterial calcification, and plaque progression. In contrast, inhibition of NF-κB signaling has been shown to protect against atherosclerosis. This chapter aims to discuss recent progress on the roles of NF-κB in lipid metabolism and atherosclerosis and also to highlight its potential therapeutic benefits.