Atherosclerosis, characterized by excess lipid deposition and chronic inflammation, is the common pathological basis of cardiovascular diseases. Macrophages, as important immune cells, are involved in the entire process of atherosclerosis. Recent studies have shown that macrophage efferocytosis is a homeostatic mechanism responsible for the clearance of dead/apoptotic cells and the resolution of inflammation. In atherosclerosis, the capacity of macrophages to participate in efferocytosis is hampered, resulting in the abnormal accumulation of apoptotic cells and necrotic tissue within the plaques, which leads to the enlargement of necrotic core, increased luminal stenosis, plaque inflammation, and ultimate plaque destabilization or rupture. In this review, we summarized the efferocytic machinery that is normally implicated in cardiovascular physiology and then highlighted the mechanisms by which efferocytosis fails in atherosclerosis, aiming to provide therapeutic approaches for this pathological process.