The transport and functions of biologically active naturally occurring retinoids (Vitamin A, retinol, and its metabolites) are mediated by extracellular, intracellular, and nuclear proteins. X-ray crystallographic studies to date on the extra- and intracellular proteins have helped to define distinct protein retinoid recognition mechanisms, each with a characteristic structural motif. The extracellular proteins (serum retinol-binding protein and a retinoic acid-binding protein from rat epididymis) bind retinoids with a hand-in-glove like fit in deep, hydrophobic-binding cavities. The intracellular proteins (cellular retinol-binding proteins types I and II) encapsulate the ligand in an aqueous internal cavity. The details of the mechanisms of retinoid recognition, and how they result as a consequence of the different protein structures, are described in this review.