The signaling pathways that control the life-death switch of a cell are a prime interest in Modern Biology. To this respect, NF-kappaB has emerged as a decisive transcription factor in the cell's response to apoptotic challenge and its effects on apoptosis have far-reaching consequences for normal development and/or homeostasis in many cells and tissues, including the immune system, hair follicles, and epidermal appendages, the liver, and nervous system. In this review we analyze the pivotal role of the transcription factor NF-kappaB in the normal functioning of the cardiac cell and its implication on some of the most frequent cardiac pathologies, such as ischemia-reperfusion injury, ischemic precondition, hypertrophy, atherosclerosis and cardiac arrest. While NF-kappaB is commonly found to be cytoprotective, there are a number of instances where it is proapoptotic depending on the inducing stimulus and the cell context. Significant progress has been made in understanding its mode of action and its interplay with other key factors. These studies identified many anti- and pro-apoptotic NF-kappaB regulated genes that mediate its activity, these important new insights fuel hope that novel approaches will be developed to control the effects of NF-kappaB in cardiac pathologies.