Calprotectin is a calcium binding protein produced by neutrophils and monocytes locally at the site of inflammation in order to trigger the innate immunity receptors. This unique characteristic makes it a good proxy for evaluation of local inflammation in chronic inflammatory rheumatic diseases. Complete data suggest, in inflammatory rheumatic diseases, a relevant role of calprotectin in the inflammatory process. The interest of serum or plasma calprotectin dosage has been studied intensively, in the current years, especially in rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis and ANCA associated vasculitis. Calprotectin seems to be a great candidate as biomarker to assess and monitor disease activity, to predict structural progression or response to the treatment. Calprotectin showed its ability to predict radiological progression in rheumatoid arthritis and ankylosing spondylitis. Serum calprotectin can predict the risk of relapse in ANCA associated vasculitis and the risk of inflammatory bowel disease in spondyloarthritis. Nevertheless, studies report controversial result requiring replication in other large cohort. The lack of assay standardization between studies is a problem to replicate and compare studies. In this review, we discuss on the interest of systemic calprotectin in chronic inflammatory rheumatic disease as a diagnostic, activity or prognostic biomarker.