 The M2 macrophages are immune cells with diverse functions that govern immunity, tissue homeostasis, metabolism, and endocrine signaling, and can be identified by a set of markers including transmembrane glycoproteins, scavenger receptors, enzymes, growth factors, hormones, cytokines, and cytokine receptors. The review discusses the reliability of these markers in identifying M2 macrophages and their functional subdivisions, as well as updates on the tissue environment and neuroendocrine system signals that shape M2 activation and possible evolutionary routes of their functions. This article was authored by Thomas Risser.