The diagnosis of periprosthetic joint infection (PJI) has been performed by obtaining a history and physical examination, blood tests, and analysis of the synovial fluid and tissue samples. The measurement of serum biomarkers are routinely used to diagnose PJI. These markers may be elevated in other inflammatory conditions, necessitating the need for more specific biomarkers to diagnose PJI. Serum biomarkers may be more specific to PJI. Synovial CRP, α-defensin, human β-defensin-2 and -3, leukocyte esterase, and cathelicidin LL-37 biomarkers hold promise for the diagnosis of PJI.