There is little direct evidence how monocytes and tissue macrophages contribute to asymptomatic infection, but their tissue distribution, receptor repertoire and secretory capacity are vital to viral resistance as well as dissemination. Acute macrophage antiviral and inflammatory responses determine the outcome of infection, together with other innate and adaptive host mechanisms. We outline evidence from clinical [20] and experimental observations from earlier [51] and current [20] coronavirus studies and consider the role of macrophages and monocytes in local and systemic infections, the antiviral and inflammatory response, resolution and complications.