Oligodeoxynucleotides, ribozymes, and RNA interference make part of the antisense strategy, a new tool proposed to conquer cancer, viral infections, as well as cardiovascular and rheumatic diseases. The silencing effect of antisense strategies is both highly specific and potent - and only requires that the sequence of the target RNA is known. However, so far neither RNAi nor ribozymes have been approved for clinical use and only a single antisense agent is on the market. In the context of degenerative joint diseases, experimental data in the field of antisense strategies are still rare. Several studies from rheumatoid arthritis (RA), an inflammatory condition that leads to the progressive destruction of cartilage and bone within affected joints, however revealed promising results and taught us important lessons that might also be useful in therapeutic approaches for osteoarthritis (OA). To introduce these therapies in clinical practice, however, several hurdles still have to be overcome.