Macrophages are important to immune function and also actively participate in iron homeostasis. The involvement of splenic and liver macrophages in the processing of effete erythrocytes and the subsequent return of iron to the circulation is well established, and the molecular details of iron recycling have been characterized recently. Another important aspect regarding iron handling by macrophages is their capacity to act as immune cells, which involves the inflammatory response, as well as other pathological conditions in which macrophages are central. This review discusses the latest advances in macrophage iron trafficking and the pathophysiological consequences of altered iron homeostasis in these cells.