Important advances in our understanding of iron metabolism have been made during the past 10 years, highlighting the mechanisms by which dysregulated iron homeostasis leads to hematologic, metabolic, and neurodegenerative diseases. In particular, the discovery of hepcidin and its fundamental role as the hormonal peptide regulating iron metabolism has delineated the organization of the complex network of proteins that regulates iron metabolism within the body. Maintenance of iron homeostasis is the consequence of tight coordination between iron absorption from the diet by enterocytes, and iron recycling by macrophages following degradation of senescent erythrocytes. Thus, any perturbation of these processes leads to a wide spectrum of diseases, ranging from iron deficiency anemia to iron overload. This review will focus particularly on the mechanisms involved in iron recycling by macrophages and summarize the pathological conditions perturbing this process.