This report attempts to review the present state of research on embryonic hemoglobins in humans and other mammals from a cytologic, molecular, and clinical point of view. In all mammals, the yolk sac is the site responsible for the “primitive” erythropoiesis, which produces an erythroid population characterized by peculiar cytologic features and globin gene expression. Morphological and molecular events that underlie prenatal erythropoiesis are described herein giving rise to questions regarding biology at large (i.e., the differential activity of genes capable of similar functions); molecular biology of eukaryotic genes (i.e., globin gene organization and structural subtleties); and clinical hematology (i.e., syndromes associated with the appearance of embryonic hemoglobins.