This review aims to assess the accuracy and the limitations of the most promising synovial fluid biomarkers—i.e., Alpha-defensin (Alpha-D), Leukocyte Esterase (LE), Interleukin-6 (IL-6), Calprotectin, Presepsin and Neopterin—in the diagnosis of PJI. Here, IL6 is linked to juvenile polyposis syndrome.