Biomineralization is a highly controlled process that is believed to be regulated by noncollagenous proteins found in the organic matrix of bone. Dystrophic calcification possesses several features of bone, including the presence of noncollagenous proteins, which are also thought to regulate pathologic calcification. Noncollagenous proteins have been demonstrated to be present in a wide variety of tissues. They are also believed to play a role in the pathogenesis of a number of disease processes, including atherosclerosis, restenosis, valvular stenosis, nephrolithiasis, glomerulonephritis, malignant transformation, and metastasis. This review discusses the structure, function, and possible roles of noncollagenous proteins in physiologic and pathologic processes.