The main line of defense that exists to eliminate foreign agents falls on phagocytic cells (neutrophils, dendritic cell, and macrophages), and it does so through phagocytosis, a complex cellular mechanism that occurs after the recognition and binding of the ligand by cellular receptors. Macrophages are part of a diverse lineage of innate immune cells. Once a macrophage receptor binds its ligand, a coordinated intracellular signaling cascade is activated to the clearance or otherwise of the foreign agent. Objects removed by macrophage phagocytosis include dead or dying host cells, cells opsonized with antibodies, and specific pathogens such as bacteria, fungi, parasites, and viruses. Currently, phagocytic macrophages have been shown to contribute to the killing of cancer cells, inflammatory bowel disease, atherosclerosis, Alzheimer’s disease, and schizophrenia. For this reason, phagocytic macrophages are important in critical participation for health and disease.