Periprosthetic shoulder infection (PSI) remains a devastating complication after total shoulder arthroplasty (TSA). Furthermore, there is a paucity in the literature regarding its diagnostic and therapeutic management, especially the absence of therapy concepts devised exclusively for PSI. The aim of the presenting study is to examine the characteristics and outcome of patients with PSI who were treated according to well-established algorithms developed originally for periprosthetic joint infection (PJI) of the hip and knee and determine if these algorithms can be applied to PSI. This single-center case series included all patients with a PSI presenting between 2010 and 2020. Recorded parameters included age, sex, affected side, BMI, ASA score, Charlson comorbidity index, preoperative anticoagulation, indication for TSA (fracture, osteoarthritis or cuff-arthropathy), and type of infection (acute or chronic PSI). The outcome was divided into treatment failure or infect resolution. Staphylococcus epidermidis and aureus were the commonest infecting pathogens. Acute PSI was mainly treated with debridement, irrigation, and retention of the prosthesis (DAIR) and chronic cases with two/multiple-stage exchange. The treatment failure rate was 10.5%. C-reactive protein was preoperatively elevated in 68.4% of cases. The mean number of operative revisions was 3.6 ± 2.6, and the mean total duration of antibiotic treatment was 72.4 ± 41.4 days. The most administered antibiotic was a combination of clindamycin and fluoroquinolone. In summary, the data of the current study suggest that therapeutical algorithms and recommendations developed for the treatment of PJI of the hip and knee are also applicable to PSI.