Biomineralization is characterized by a high degree of control over the location, nature, size, shape, and orientation of the crystals formed. For many years, it has been widely believed that the exquisitely precise nature of crystal formation in biological tissues is the result of stereochemically specific interactions between growing crystals and extracellular matrix proteins. That is, the ability of many mineralized tissue proteins to adsorb to particular faces of biominerals has been attributed to a steric and electrical complementarity between periodic regions of the polypeptide chain and arrays of ions on the crystal face. In recent years, however, evidence has accumulated that many mineral-associated proteins lack periodic structure even when adsorbed to crystals. It also appears that protein-crystal interactions involve a general electrostatic attraction rather than arrays of complementary charges. In the present work, we review these studies and present some relevant new findings involving the mineral-modulating phosphoprotein osteopontin. Using molecular dynamics simulations, we show that the adsorption of osteopontin peptides to hydroxyapatite crystals does not involve a unique conformation of the peptide molecule, and that the adsorbed peptides are not aligned with rows of Ca(2+) ions on the crystal face. Further, we show that the interface between osteopontin peptides and calcium oxalate monohydrate crystals consists of peptide regions of high electronegativity and crystal faces of high electropositivity. Collectively, the above-mentioned studies suggest that interactions between mineral-modulating proteins and biologically relevant crystals are primarily electrostatic in nature, and that molecular disorder assists these proteins in forming multiple bonds with cations of the crystal face.