Many cells and their cytokines play critical roles in the development of RA. The synovial compartment is infiltrated by leukocytes and the synovial fluid is inundated with pro-inflammatory mediators that are produced to induce an inflammatory cascade, which is characterized by interactions of fibroblast-like synoviocytes with the cells of the innate immune system, including monocytes, macrophages, mast cells, dendritic cells, and so on, as well as cells of adaptive immune system such as T cells and B cells. Endothelial cells contribute to the extensive angiogenesis. The fulminant stage contains hyperplastic synovium, cartilage damage, bone erosion, and systemic consequence. Bone resorption virtually creates bone erosions, which are usually found at spots where the synovial membrane inserts into the periosteum, which is known as a bare area according to certain anatomical features. The destruction of the subchondral bone can eventually result in the degeneration of the articular cartilage as the result of a decrease in osteoblasts and an increase in osteoclasts and synoviocytes. IL interleukin, TNF tumor necrosis factor, MMP matrix metalloproteinase, TGF transforming growth factor, PDGF platelet-derived growth factor, IFN interferon, GM-CSF granulocyte–macrophage colony-stimulating factor, VEGF vascular endothelial growth factor, FGF fibroblast growth factor.