Publisher Summary This chapter describes the role of messenger RNA (mRNA) stability in the control of globin gene expression during the terminal differentiation of erythroid cells, and summarizes recent findings that define the corresponding crucial cis- and trans-acting determinants. It also discusses the contribution of globin mRNA stability to the embryonic-to-fetal and fetal-to-adult switches in globin gene expression. The cells of erythroid lineage display three unique characteristics distinguishing them from other hematopoietic cells. First, erythroid cells contain extraordinarily high levels of the oxygen transport molecule, hemoglobin. Second, the expression of constituent globin subunits switches at two points during human ontogeny. Third, the terminal stages of erythroid differentiation occur in cells that have undergone global, irreversible transcriptional arrest. The cellular concentration of a particular mRNA species is determined by the balance between its rates of synthesis and degradation. Erythropoeisis can be segmented into six stages on the basis of conventional histologic staining and light microscopy. The realization that mRNA stability can have a profound impact on gene expression and on cellular phenotype leads to speculation on potential novel therapeutic applications.