Through recent research, there has been a significant number of findings involving the biology of macrophages. Beyond the 1st line of defense, macrophages have several specific characteristics across different tissues, organs, and systems. Macrophages comprehend a heterogeneous phagocytic population with wide range phenotypes, and tissue-specific functions, such as bone resorption, extracellular matrix production, red blood cells and bacteria removal, among others. Through innate immune receptors macrophages can modulate several pathways that culminate in the production of various types of inflammatory mediators such as chemokines, cytokines, oxygen reactive species, and lipid mediators which ultimately altered the behavior of other cells. Moreover, environment signals modify and induce metabolic reprograming that it alters phenotype and functions.