Iron is an essential trace element required for human health,^[1] but both deficiency and excess can lead to adverse outcomes influenced by dietary intake, genetics, and absorption, with a significant global burden where approximately one in four women is affected by iron deficiency. Assessing iron status is complex because iron homeostasis involves tightly regulated intestinal absorption and distribution across three key compartments—iron stores, transport iron, and functional iron—where depletion of each reflects progressive stages of deficiency. Biochemical evaluation relies mainly on serum-based indicators such as ferritin, transferrin saturation (TSAT), and soluble transferrin receptor (sTfR), although these markers are traditionally more useful for detecting deficiency than iron overload or repletion. Ferritin reflects body iron stores despite representing a small fraction of total iron, while bone marrow iron staining remains the gold standard but is not practical for routine use; early depletion of ferritin indicates iron depletion even before anemia develops. The sTfR-to-ferritin ratio integrates early and late changes in iron deficiency, while emerging markers such as hepcidin provide insight into iron regulation but are limited by variability, lack of standardization, and sensitivity to inflammation.^[2] Inflammatory states further complicate interpretation because ferritin behaves as an acute-phase reactant, masking true iron deficiency and making differentiation between iron deficiency anemia (IDA) and anemia of inflammation (AI) challenging. Cytokines such as IL-6 and TNF-α increase hepcidin, reducing intestinal iron absorption and trapping iron in macrophages, leading to functional iron deficiency despite adequate stores. IDA results from inadequate iron supply due to poor intake, blood loss, or malabsorption and is treated with iron replacement and correction of underlying causes, whereas AI arises from chronic inflammatory conditions and is managed by treating inflammation, modulating hepcidin pathways, and using selective iron or erythropoiesis-stimulating therapies. Overall, accurate diagnosis requires integrated interpretation of multiple biomarkers, as no single test fully captures the complexity of iron metabolism across health and disease.