Focal buildup of cholesterol in arteries is the process that produces atherosclerotic plaques, the cause of most coronary artery disease and strokes. Monocyte-derived macrophages are central cells that accumulate this cholesterol in atherosclerotic lesions, a manifestation of the scavenging function of the macrophage. Different types of cholesterol-containing lipid particles found in atherosclerotic lesions may enter macrophages by a variety of endocytic pathways. The fate of cholesterol that enters macrophages determines whether macrophages help or hinder cholesterol removal from the vessel wall. Macrophages may function to carry cholesterol out of lesions, or to process the cholesterol for excretion in association with small protein-phospholipid complexes. Alternatively, macrophages that do not efficiently function to remove cholesterol from lesions may ultimately undergo cell death. Some cytokines, hormones, and pharmacologic agents show potential to modulate these processes and may be useful in directing macrophage function in atherosclerotic lesions towards beneficial rather than harmful effects.