The matrix metalloproteinases (MMPs) are a unique family of metalloenzymes, which, once activated, can destroy all the components of cartilage. MMPs are found in resorbing cartilage, bone, rheumatoid and osteoarthritic synovial fluid, and adjacent soft tissues. The active enzymes are all inhibited by tissue inhibitors of metalloproteinases (TIMPs). The relative amounts of active MMPs and TIMPs are important in determining whether cartilage is broken down in joint diseases. Conventional treatments for arthritis do little to affect the underlying joint destruction, but new drugs are now available that can specifically block active MMPs. These potent inhibitors prevent the destruction of cartilage both in vitro and in animal models of arthritis. Future trials in patients will test their effectiveness in the prevention of cartilage destruction.