Monocyte-derived macrophages and foam cells play a central role in atherogenesis. In vitro studies suggest that macrophages exhibit many functions relevant to lesion initiation, progression, and regression. Intimal foam cells function within an incompletely understood and complex network of cytokines, growth factors, and other mediators that vary in spatial and temporal distribution during lesion formation. Macrophages may modify lipoproteins to form derivatives that then modulate lesion formation. These cells also participate in local lipid metabolism within the atherosclerotic lesion by sequestering, processing, and exporting lipids. Macrophages participate in chronic immune and inflammatory aspects of plaque formation by elaborating a vast array of mediators, and by processing and presenting antigens to T-lymphocytes. The macrophage can elaborate both stimulators and inhibitors of smooth muscle cell migration and proliferation as well as regulate the elaboration of many constituents of the vascular matrix. Macrophages also express many of the enzymes involved in degrading matrix constituents. These cells may thereby play a central role in the remodeling of the extracellular matrix during smooth muscle cell migration, neovascularization, and plaque rupture. When a plaque is ruptured, macrophage-derived proteins that modulate blood coagulation and fibrinolysis participate in local clotting and contribute to lesion evolution as well as the transition from the chronic to the acute stages of atherosclerosis. The in vivo environment of the macrophage and foam cell is extremely complex, with multiple stimuli acting concomitantly. The information derived from in vitro studies of macrophage functions has yielded hypotheses that can now be tested in vivo using increasingly powerful experimental strategies.