Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and cartilage destruction. Fibroblast-like synoviocytes (FLS) play a crucial role in the pathogenesis of RA by producing cytokines and proteases that perpetuate inflammation and contribute to cartilage degradation. FLS exhibit an aggressive phenotype, characterized by increased invasiveness and resistance to apoptosis, which exacerbates joint damage. Recent advances in understanding the biology of FLS, including their regulation of innate immune responses and intracellular signaling mechanisms, have provided new insights into disease mechanisms. Targeting FLS could potentially complement current therapies without significantly affecting adaptive immune responses. The article discusses the normal and RA synovium, the origin and characteristics of FLS, their aggressive phenotype, and their role in cartilage destruction. It also explores the mechanisms of FLS apoptosis and their involvement in innate immunity.Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and cartilage destruction. Fibroblast-like synoviocytes (FLS) play a crucial role in the pathogenesis of RA by producing cytokines and proteases that perpetuate inflammation and contribute to cartilage degradation. FLS exhibit an aggressive phenotype, characterized by increased invasiveness and resistance to apoptosis, which exacerbates joint damage. Recent advances in understanding the biology of FLS, including their regulation of innate immune responses and intracellular signaling mechanisms, have provided new insights into disease mechanisms. Targeting FLS could potentially complement current therapies without significantly affecting adaptive immune responses. The article discusses the normal and RA synovium, the origin and characteristics of FLS, their aggressive phenotype, and their role in cartilage destruction. It also explores the mechanisms of FLS apoptosis and their involvement in innate immunity.