Nephrogenic systemic fibrosis is a new disorder reported almost exclusively in patients who have renal insufficiency and are exposed to contrast media formulated with gadolinium. High morbidity and mortality are associated with this severely disabling and painful condition. The acute phase begins upon exposure to gadolinium contrast media, characterized by a systemic inflammatory response involving iron mobilization, and then as a progressive, chronic phase in which fibrosis develops. Proposed is a unifying model of cumulative risk factors in which the interplay of systemic inflammation and stimulated hematopoietic environment associated with hyperparathyroidism and erythropoietin may tie to a common pathogenic mechanism of fibrogenesis. Because there are no uniformly effective interventions to treat nephrogenic systemic fibrosis other than successful renal transplantation, prevention by avoiding gadolinium contrast media in patients with chronic kidney disease is vital. On the basis of suspected pathogenesis, it is also reasonable to limit erythropoietin and iron therapy to dosages ensuring recommended targets and adequately control hyperparathyroidism. Herein is reviewed what is currently known about this subject.