The deposition of calcium-containing crystals in articular tissues is probably an underrecognized event. Clinical observations indicate that exaggerated and uniquely distributed cartilage degeneration is associated with these deposits. Perhaps the most compelling argument favoring a role for crystals in causing osteoarthritis stems from their in vitro effects on articular tissues. In this review, we will highlight some of the recent findings that further reinforce the thesis that basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPPD) crystals can cause the degeneration of articular tissues in 2 separate pathways. In the "Direct" pathway, crystals directly induce fibro-blast-like synoviocytes to proliferate and produce metalloproteinases and prostaglandins. The other "Paracrine Pathway" involves the interaction between crystals and macrophages/monocytes which leads to synthesis and release of cytokines which can reinforce the action of crystals on synoviocytes and/or induce chondrocytes to secrete enzymes and which eventually cause the degeneration of articular tissues.