The anemia of chronic disease (ACD) is a hypoproliferative anemia defined by a low serum or plasma iron concentration in the presence of adequate reticuloendothelial iron stores. It is been established that ACD results from the effects of cytokines that mediate the immune or inflammatory response. During the past 3 years, the clinical scope of this syndrome has been expanded beyond the traditional chronic infectious, inflammatory, or neoplastic diseases to include other, often acute, syndromes in which the same pathogenetic mechanisms are operating. An improved understanding of the use of the soluble transferrin receptor concentration in clinical medicine has enhanced the ability to diagnose ACD, and further experience with the use of recombinant human erythropoietin in the management of severely affected patients with ACD has provided a basis for rational and effective management. Ongoing studies of the mechanisms contributing to the development of ACD continue to elucidate the pathogenesis of this common and clinically significant syndrome.