Macrophages are mononuclear phagocytes with remarkable polarization ability that allow them to have tissue‐specific functions during development, homeostasis, inflammatory and infectious disease. One particular trophic factor in the tissue environment is iron, which is intimately linked to macrophage effector functions. Macrophages have a well‐described role in the control of systemic iron levels, but their activation state is also depending on iron‐containing proteins/enzymes. Haemoproteins, dioxygenases and iron–sulphur (Fe‐S) enzymes are iron‐binding proteins that have bactericidal, metabolic and epigenetic‐related functions, essential to shape the context‐dependent macrophage polarization. In this review, I describe mainly pro‐inflammatory macrophage polarization focussing on the role of iron biochemistry in selected haemoproteins and Fe‐S enzymes. I show how iron, as part of haem or Fe‐S clusters, participates in the cellular control of pro‐inflammatory redox reactions in parallel with its role as enzymatic cofactor. I highlight a possible coordinated regulation of haemoproteins and Fe‐S enzymes during classical macrophage activation. Finally, I describe tryptophan and α‐ketoglutarate metabolism as two essential effector pathways in macrophages that use diverse iron biochemistry at different enzymatic steps. Through these pathways, I show how iron participates in the regulation of essential metabolites that shape macrophage function.