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 degrees to 119 degrees (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. (C) 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.