Cathepsin K plays an essential role in bone remodeling and resorption in diseases such as osteoporosis, osteolytic bone metastasis and rheumatoid arthritis. Cathepsin K is a cysteine protease that plays a pivotal role in osteoclast function and in the degradation of protein components of the bone matrix by cleaving proteins such as collagen type I, collagen type II and osteonectin. We examined cathepsin K in the serum of 50 patients with active longstanding rheumatoid arthritis. We found increased levels of cathepsin K compared with a healthy control group and found a significant correlation with radiological destruction, measured by the Larsen score. Inhibition of cathepsin K may therefore be a new target for preventing bone erosion and joint destruction in rheumatoid arthritis. However, further studies have to be performed to prove that cathepsin K is a valuable parameter for bone metabolism in patients with early rheumatoid arthritis.