The shoulder microbiome is an emerging field in orthopedic research. Large synovial joints which were typically considered to be sterile now have strong evidence demonstrating the presence of native organisms colonizing the joint. Many of the conditions that surgeons see and treat in the shoulder, including osteoarthritis, rotator cuff tears, and adhesive capsulitis, have unclear etiology. The shoulder microbiome is a potential source of pathology in dysbiosis states, or source of protection against pathology in normobiosis states. The purpose of this review is to characterize the published research detailing the microbiome of the native shoulder joint.We conducted a systematic review and meta-analysis of data searches on Medline, Embase, Cochrane Central Register of Controlled Trials, and SCOPUS. The following search terms were used with various permutations; shoulder, skin, microbiome, infection, colonization, commensal, microbiota, flora. The terms 'shoulder' and 'shoulder AND skin' were combined with the other 6 terms for a total of 12 searches per database. Two independent reviewers conducted the review with a third reviewer available to resolve differences of interpretation. Studies were eligible if they were human studies of patients undergoing shoulder surgery (or surgical preparation therapy) with a shoulder that had not previously been operated on, where microbial samples were reported. Studies were excluded if they were systematic reviews and meta-analyses, animal studies, cadaveric studies, studies of patients under the age of 18 and studies including postoperative shoulders.The search methodology yielded 47 eligible studies for analysis, with a total of 3283 patients. Native shoulder sampling yielded positive organisms in 50.8% of all samples (95% confidence interval [CI] = 41.8%-59.8%, I 2  = 97.9%, P = .000). The predominate organism reported was C. acnes, with 29% of studies specific for C. acnes, and a total of 52 other organisms detected in the native shoulder. Skin preparation solutions reduced the skin colonization rate of 55.7% (95% CI = 32.7%-78.6%, I 2  = 98.2%, P = .000) to 43.5% (95% CI = 29.5%-57.5%, I 2  = 98.2%, P = .000). Despite the high rates of colonization detected under sterile conditions, of 42 studies and 3083 patients reporting postoperative outcomes, the infection rate was 1.8% (95% CI = 0.5%-3.2%, I 2  = 0.0%, P = .612).There is strong evidence to support the existence of a native shoulder microbiome. Further research is required to characterize this microbiome and correlate it to disease and health states.Crown Copyright © 2024 Published by Elsevier Inc. on behalf of American Shoulder and Elbow Surgeons.