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Conventional methods such as microbiological cultures may lack the sensitivity and specificity to establish definitive diagnosis of osteoarticular infections. Herein, we review the general principles and the usefulness of broad-range PCR to improve the etiological diagnosis of osteoarticular infections.Broad-range PCR followed by sequencing has been successfully developed to identify microorganisms involved in infections when patients have previously received antibiotics or in the presence of slow-growing or intracellular microorganisms. For osteoarticular infections, the studies have shown that the use of this molecular tool increased mainly the identification of Kingella kingae, anaerobic bacteria, and Streptococcus spp. However, it is very important to underline that the interpretation of this molecular tool is critical because of several pitfalls, including contamination causing false-positive results.Broad-range PCR followed by sequencing offers several advantages when used to complement culture results for the diagnosis of fastidious bacteria and for patients taking antibiotics. However, its use should be restricted mainly for culture-negative cases when infection is suspected on the basis of clinical signs and symptoms or inflammatory syndrome. Future developments will include the use of real-time PCR in a closed system and pathogen-specific PCR for the molecular diagnosis of osteoarticular infections.