One of the most important contributions to the vitamin D field has been the discovery by Wasserman and Taylor in 1966 (1) of vitamin D-dependent calcium binding protein [calbindin-D (2)]. Early studies using competitive ion exchange methods as well as equilibrium dialysis indicated that administration of vitamin D to rachitic chicks resulted in an increase in the calcium binding activity of crude extracts of intestinal mucosa (1). Further investigations showed that the calcium binding activity was associated with a protein of about 28,000 mol wt (3, 4). Soon after the discovery of avian intestinal calbindin (1), a vitamin D-responsive calcium binding protein was also shown to be present in rat intestine (5, 6). Since the initial discoveries of the avian and rat intestinal calbindins, calbindins have been reported in a variety of species (7–19) and in many other tissues including kidney (20–25), bone (26), and tissues which are not regulators of serum calcium such as pancreas (27–32), placenta (33, 34), and brain (35–40). Several of these proteins have been isolated and biochemically characterized. In addition, antisera against a few of these proteins have been developed, which provide a tool for their assay and a means of determining their localization. Hypotheses concerning the functional significance of the calbindins, based on immunocytochemical localization studies, have been presented. Although the exact physiological function of calbindin is unknown at this time, regulation of its biosynthesis has provided an important model for studying the molecular mechanisms of action of the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D³ (1,25(OH)²D³). 1,25-(OH)²D³ is concentrated in target cells by stereospecific binding to a high affinity receptor protein in the target cell nucleus, resulting in the expression of genetic information coding for calbindin (41, 42).