Macrophages are central to both innate and adaptive immunity. With few exceptions, macrophages are the first cells that sense trouble andrespond to disturbances in almost all tissues and organs. They sense their environment, inhibit or kill pathogens, take up apoptotic and necrotic cells, heal tissue damage, and present antigens to T cells. Although the origins (yolk sac versus monocyte-derived) and phenotypes (functions, gene expression profiles, surface markers) of macrophages vary betweentissues, they have many receptors in common that are specific to one ora few molecular species. Here, we review the expression and function ofalmost 200 key macrophage receptors that help the macrophages sense what is going on, including pathogen-derived molecules, the state of the surrounding tissue cells, apoptotic and necrotic cell death, antibodies and immune complexes, altered self molecules, extracellular matrix components, and cytokines, including chemokines.