Granulocyte macrophage-colony stimulating factor (GM-CSF) blockade and that of its receptor are effective in inflammatory arthritis models and rheumatoid arthritis trials. We have discovered a GM-CSF/CCL17 pathway in monocytes/macrophages. The putative role of this pathway in both inflammatory arthritis and osteoarthritis (OA) pain and disease, including in obesity-associated OA, will be discussed. Ideas on the mode of action of CCL17, including its possible involvement in fibrosis/fibroblast biology, will also be presented. In contrast to the well-recognized chemotactic role of CCL17 (e.g. preferential Th2 cell chemotaxis), these data reveal a lymphocyte-independent, non-chemotactic and algesic role of CCL17 in arthritis and possibly other indications, and suggest that it could be a potential therapeutic target in inflammatory pain and disease.