Tissue culture should remain the gold standard for microbiological diagnosis of shoulder periprosthetic joint infection (PJI). Combination of serum D-dimer and serum C-reactive protein (CRP) might be utilized as a confirmatory test in the diagnosis of shoulder PJI but not to rule out infection. Preoperative arthroscopic tissue biopsy utilized for microbiology cultures might be an emerging useful tool to help guide the management of PJI of the shoulder. Preoperative positive aspiration culture (synovial fluid) has favorable sensitivity and specificity when compared with intraoperative tissue cultures in identifying pathogenic microorganisms in individuals with shoulder PJI. However, the overall high rate of discordance between preoperative and intraoperative culture might prompt surgeons to base medical and surgical management on patient history and other factors and avoid relying solely on preoperative synovial fluid culture data.