S100A8/A9, also known as calprotectin or MRP8/14, is a heterocomplex of the two S100 calcium binding proteins, S100A8 (calgranulin A or MRP8 – myeloid related protein 8) and S100A9 (calgranulin B or MRP14 – myeloid related protein 14). S100A8 has a molecular weight of 11.0 kDa and S100A9 exists in two forms, 13.3 kDa and truncated 12.9 kDa. Both proteins are similar to other members of the S100 family in that they contain two EF-hand motifs that bind calcium ions. Ca2+-binding induces the formation of heterocomplexes S100A8/S100A9 and (S100A8)2 /(S100A9)2. S100A8 and S100A9 are expressed in a tissue/cell-specific manner mainly in cells of the myeloid lineage, such as granulocytes, monocytes and early stages of macrophages, but not in resident tissue macrophages. They are also expressed in keratinocytes and epithelial cells but only under inflammatory conditions. S100A8/A9 complex is an antimicrobial peptide that is released by innate immunity cells immediately after host pathogen interaction, protects cells against invasive microorganisms, and regulates adhesion of leucocytes to the endothelium and extracellular matrix during the inflammatory process. S100A8/A9 has emerged as a very promising biomarker for a wide range of inflammatory processes such as rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, inflammatory bowel disease (IBD), acute lung inflammation and vasculitis. Fecal S100A8/A9 level reflects the severity of mucosal inflammation and is a good diagnostic marker for monitoring of IBD (Crohn’s disease, ulcerative colitis) and neoplasm. S100A8/A9 serum levels have been identified as independent risk predictors for various cardiovascular diseases such as acute coronary syndrome and myocardial infarction. High circulating levels of S100A8/A9 complex were measured in patients with abdominal adiposity and correlated with visceral fat area, body mass index, subcutaneous fat area, and leukocyte count. S100A8 and S100A9 play a critical role in tumor biology and their elevated levels were found in numerous tumors. In cancer progression low concentrations of S100A8/A9 complexes promote tumor cell growth and tumor cell migration, while high concentrations are associated with apoptotic effects on tumor cells. Measuring urinary calprotectin shows potential in the differential diagnosis of acute kidney injury (AKI).