Abstract Nuclear factor kappa-B (NFκB), a redox-sensitive transcription factor regulating a battery of inflammatory genes, has been indicated to play a role in the development of numerous pathological states. Activation of NFκB induces gene programs leading to transcription of factors that promote inflammation, such as leukocyte adhesion molecules, cytokines, and chemokines, although some few substances with possible anti-inflammatory effects are also NFκB regulated. The present article reviews basic regulation of NFκB and its activation, cell biological effects of NFκB activation and the role of NFκB in apoptosis. Evidence involving NFκB as a key factor in the pathophysiology of ischemia-reperfusion injury and heart failure is discussed. Although activation of NFκB induces pro-inflammatory genes, it has lately been indicated that the transcription factor is involved in the signaling of endogenous myocardial protection evoked by ischemic preconditioning. A possible role of NFκB in the development of atherosclerosis and unstable coronary syndromes is discussed. Nuclear factor kappa-B may be a new therapeutic target for myocardial protection.