Diagnosis of implant-related (periprosthetic joint) infections poses a major challenge to infection disease physicians and orthopaedic surgeons. Conventional diagnostic tests continue to suffer from issues of accuracy and feasibility. Biomarkers are used throughout medicine for diagnostic and prognostic purposes, as they are able to objectively determine the presence of a disease or a biological state. There is increasing evidence to support the measurement of specific biomarkers in serum and/or synovial fluid of patients with suspected periprosthetic joint infections. Promising serum biomarkers include interleukin (IL)-4, IL-6, tumour necrosis factor (TNF)-α, procalcitonin, soluble intercellular adhesion molecule 1 (sICAM-1), and D-dimer. In addition to c-reactive protein and leucocyte esterase, promising biomarkers that can be measured in synovial fluid include antimicrobial proteins such as human β-defensin (HBD)-2 and human β-defensin (HBD)-3, and cathelicidin LL-37, as well as several interleukins such as IL-1β, IL-6, IL-8, IL-17, TNF- α, interferon-δ, and vascular endothelial growth factor.