Inflammation in joint tissues is one of the causes of early mortality in rheumatological diseases. In fact, inflammation process is followed by cell infiltration, synovial tissue proliferation, cartilage and bone destruction. Therefore, various studies have been done to understand the pathogenesis and biochemical mechanisms of inflammation. Specifically, relationship between S100 protein family and inflammation in some type of rheumatologic diseases constitute the basis of this review. Scientific evidences emphasis a crucial role for S100 proteins in acute and chronic inflammatory diseases and also have been proposed as useful biomarkers of certain types of rheumatological diseases.