Biological iron is needed but hazardous to organisms. This dual effect prompted numerous researchers to examine the mechanisms controlling its homeostasis in pathologic circumstances. The discovery of genes responsible for hereditary illnesses like hemochromatosis, the IRE/IRPs machinery, and the hepcidinferroportin axis has increased our understanding of iron metabolism. Deregulation of iron homeostasis, inflammation, and oxidative stress are often generated by iron buildup in pathologic situations. To provide a current state-of-the-art on the importance of iron in pathophysiologic conditions, we promoted a Research Topic with the contributions of top-leading scientists who studied the effects of iron homeostasis disruption on genetic, inflammatory, infectious, cardiovascular, and neurodegenerative diseases. This topic attracts some of the world's most eminent researchers, all of whom are dedicated to expanding our understanding of iron metabolism and its function in a wide range of human disorders.