Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic, chronic joint inflammation. In spite of great efforts, the etiology of RA has not been completely elucidated to date. Toll-like receptors (TLRs) belong to the family of pattern recognition receptors and are involved in both innate and adaptive immune responses against microorganisms via recognition of pathogen-associated molecular patterns. In addition, TLRs have been reported to recognize several endogenous ligands, which are generated under stress conditions and cartilage damage. Triggering of TLRs results in the release of various proinflammatory cytokines such as IL-1β and tumor necrosis factor alpha. IL-1β is one of the crucial cytokines in the pathogenesis of RA and is involved in Th1-mediated processes and cartilage and bone destruction. Therefore, TLRs may potentially be involved in either initiation or chronicity of arthritis.