Monocytes are circulating blood leukocytes that play important roles in the inflammatory response, which is essential for the innate response to pathogens. But inflammation and monocytes are also involved in the pathogenesis of inflammatory diseases, including atherosclerosis. In adult mice, monocytes originate in the bone marrow in a Csf-1R (MCSF-R, CD115)-dependent manner from a hematopoietic precursor common for monocytes and several subsets of macrophages and dendritic cells (DCs). Monocyte heterogeneity has long been recognized, but in recent years investigators have identified three functional subsets of human monocytes and two subsets of mouse monocytes that exert specific roles in homeostasis and inflammation in vivo, reminiscent of those of the previously described classically and alternatively activated macrophages. Functional characterization of monocytes is in progress in humans and rodents and will provide a better understanding of the pathophysiology of inflammation.