Point mutations in Ca2+-binding sites of extracellular matrix proteins have been identified as the cause of human disorders such as Marfansyndrome and pseudoachondroplasia. Although the modes of Ca2+ binding and the effects of point mutations are not yet understood in these two cases, new insight was recently gained by X-ray and NMR structure determinations of several other extracellular proteins; these studies revealed a diversity of functions of Ca2+ ions. Ca2+ may induce a profound conformational change within a single domain, may bridge adjacent domains and thus direct the relative domain orientation and supramolecular structure, or may be involved in carbohydrate and membrane binding.