AbstractPhagocytosis is the process of recognition and engulfment of microorganisms or tissue debris that accumulate during infection, inflammation or wound repair. This ingestion, which is performed most efficiently by migrating, bone marrow‐derived cells called ‘professional phagocytes’, is essential for successful host defense. Ingestion results when an invading microorganism is recognized by specific receptors on the phagocyte surface and requires multiple, successive interactions between the phagocyte and the target. Each of these interactions results in a signal transduction event, which is confined to the membrane and cytoskeleton around the ligated receptor and which is required for successful phagocytosis. Many molecules found at sites of inflammation or infection stimulate phagocytosis, so that efficient ingestion is confined to the site of infection or inflammation, which in turn limits the proinflammatory and tissue‐destructive processes that accompany phagocytosis. This review summarizes current understanding of this critical component of host defense and of its regulation.