Periprosthetic joint infection (PJI) is a feared complication occuring in 0.5-2% of the patients after knee or hip arthroplasty. The type of surgical management widely depends on the etiologic diagnosis of the pathogen. Almost any bacterial or fungal pathogen may cause PJI. However, in 5-10% of the cases even sophisticated culture techniques remain negative. In addition, in a group of patients with so-called aseptic loosening of the device, failure may be caused by undetected microorganisms. Since specific long-term treatment is needed for successful outcome, knowledge of the etiologic agent is of great importance. Metagenomics has the potential to identify pathogens which cannot be detected by conventional culture.