The diagnosis of a fracture-related infection (FRI) can be difficult due to the lack of early diagnostic tests with high sensitivity and specificity. Diagnosis is currently based on the 2018 AO-EBJIS consensus, which establishes four confirmatory criteria and multiple suggestive criteria. Preoperative diagnosis is mostly based on clinical confirmatory criteria (presence of a fistula, sinus, or wound breakdown, or the presence of pus or purulent discharge). Intraoperative confirmation of FRI is possible with histopathological analysis (presence of microorganisms in deep tissue samples confirmed by specific staining techniques for bacteria and fungi, or presence of >5 polymorphonuclear neutrophils per high-power field). The gold standard for FRI diagnosis is identification of two phenotypically indistinguishable pathogens by culture from at least two deep tissue samples. Targeted antibiotic therapy will be based on culture results, so adequate sample collection is essential. Suggestive criteria include clinical (local or systemic signs of infection), radiological (osteolysis, implant loosening, sequestration, nonunion, involucrum, etc.) and laboratory (abnormal behavior of inflammatory biomarkers over time) signs. The presence of suggestive criteria should prompt further investigation to look for confirmatory criteria. The threshold for surgical exploration should be low.