Macrophages play a central role in atherosclerotic plaque destabilization, leading to acute coronary syndromes and sudden death. Removal of macrophages from plaques via pharmacological therapy may therefore represent a promising approach to stabilize vulnerable, rupture-prone lesions. In this review, we summarize the current therapeutic means to induce macrophage cell death in atherosclerotic plaques without affecting smooth muscle cell viability, and their potential pitfalls.