Osteoarthritis or 'Joint Failure' is a multi-factorial disease with a final common pathway of cartilage degeneration and bone eburnation. The association of arthritic disease and joint degeneration with the deposition of sodium urate crystals in gout and calcium pyrophosphate crystals in pseudogout (chondrocalcinosis) is clinically well established. Electron microscopy coupled with electron probe analysis has revealed the presence of various other calcium phosphate crystals in joint tissues and fluids. We have found three new morphological types of apatite crystals in human articular cartilage which are too small to be detected by X-rays of human joints or even by light microscopy of joint tissues. Two morphologically distinct types of apatite crystals in articular cartilage are associated with extracellular matrix vesicles formed from the cell processes of chondrocytes. 'Cuboid' crystals, which are found in the pericellular regions near the surface zone of articular cartilage, appear to be a variant of apatite and may even be 'Whitlockite' because there are traces of magnesium present. There are increased numbers of these microscopic 'cuboid' crystals (Type II) and Mineral Nodules (Type I) in arthritic cartilage and this is coupled with increased numbers of matrix vesicles and alkaline phosphatase activity. Clusters of fine needle-shaped apatite crystals (Type III) found on the surface of articular cartilage are not associated with matrix vesicles. Thus some forms of osteoarthritis are closely associated with apatite type crystal deposition and may imply abnormal mineral formation in articular cartilage as a pathogenic mechanism.