Background Periprosthetic shoulder infections (PSIs) are challenging to treat and often result in significant patient morbidity. Without a standardized treatment protocol, PSIs are often managed similarly to periprosthetic hip and knee infections. Because 2-stage revision is the gold standard for treating periprosthetic hip and knee infections, we performed a case series and literature review to determine its effectiveness in PSIs. Methods We identified 19 patients (14 men) from our institution who were treated with a 2-stage revision after presenting with a PSI. Mean patient age was 63 ± 9 years, and average body mass index was 30.8 ± 5.8. The average time from the index arthroplasty to treatment was 40 months, 8 of 13 positive cultures were Propionibacterium acnes , and 9 of 19 patients had multiple shoulder operations before presenting with infection. Minimum follow-up for all patients was 2 years. Results After a mean follow-up of 63 months (range, 25-184 months), 15 of 19 patients in our study were successfully treated for PSI. Average postoperative American Shoulder and Elbow Surgeons (ASES) Shoulder Assessment score was 69 (range, 32-98) and average postoperative forward elevation was significantly increased from 58° to 119° ( P  < .001). The incidence of recurrent infection was 26%. The rate of noninfection complications was 16%, for a total complication rate of 42%. Conclusion In patients with PSIs, especially those with intractable, chronic infections, a 2-stage revision represents a viable treatment option for eradicating infection and restoring function. However, it is important to recognize the risk of recurrent infection and postoperative complications in this challenging patient population.