Soluble transferrin receptor (sTfR), one of the main regulators of cellular iron homeostasis, is the truncated form of the tissue receptor that is encoded by the human TfR gene (chromosome 3). Serum sTfR levels are determined to detect iron deficiency (ID) in inflammatory states and in anemia of chronic disease (ACD) and to monitor the efficiency of erythropoietin (EPO) treatment. The levels of sTfR reflect the receptor density on cells (tissue iron status) and the number of cells with receptors (erythropoietic activity). Currently assays for the measurements of sTfR are standardized using different reference materials, give different results, and have different reference ranges. The recent development of a lyophilized preparation of recombinant soluble transferrin receptor (rsTfR) as a World Health Organization (WHO) reference reagent should help in the standardization of sTfR immunoassays. This article reviews the general characteristics of (s)TfR, the assays for sTfR, biological confounders in the assays, and the clinical applications for measuring sTfR.