Originally recognized as an essential part of the innate and acquired immune systems, macrophages emerged as omnipresent and influential regulators of embryo- and organo-genesis, as well as of tissue and tumor growth. Macrophages are present essentially in all tissues, beginning with embryonic development and, in addition to their role in host defense and in the clearance of apoptotic cells, are being increasingly recognized for their trophic function and role in regeneration. Some tissue macrophages are also found to possess a substantial potential for autonomous self-renewal. Macrophages are associated with a significant proportion of malignant tumors and are widely recognized for their angiogenesis-promoting and trophic roles, making them one of the new promising targets for cancer therapies. Recent expression profiling of embryonic macrophages from different tissues revealed remarkable consistency of their gene expression profiles, independent of their tissue of origin, as well as their similarities with tumor-associated macrophages. Macrophages are also capable of fusion with other cells in tissue repair and metastasizing tumors, as well as with each other in the immune response and osteoclastogenesis.