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Despite tremendous advances over the last 15 years in identifying vulnerable atherosclerotic plaques, the incidence of death and disability caused by such lesions still remains the number one health threat in developed countries. Therefore, new systemic or focal therapies aimed at decreasing the overall burden of disease, and a change to a more benign phenotype, are needed. Because cell death is a prominent feature of advanced atherosclerotic plaques with a major impact on plaque destabilization, an increasing number of compounds targeting the apoptotic or autophagic machinery in atherosclerosis are being explored, predominantly at the preclinical level. This review will provide an overview of these compounds, with a focus on both inhibition and stimulation of cell death, to prevent acute coronary syndromes and sudden cardiac death.