Atherosclerosis is a chronic inflammatory vascular disease and a leading cause of death worldwide. Macrophages play an important role in inflammatory responses, cell-cell communications, plaque growth and plaque rupture in atherosclerotic lesions. Here, we review the sources, functions and complex phenotypes of macrophages in the progression of atherosclerosis, and discuss the recent approaches in modulating macrophage phenotype and autophagy for atherosclerosis treatment. We then focus on the drug delivery strategies that target macrophages or use macrophage membrane-coated particles to deliver therapeutics to the lesion sites. These biomaterial-based approaches that target, modulate or engineer macrophages have broad applications for disease therapies and tissue regeneration.