The use of shoulder arthroplasty is continuing to expand. Periprosthetic joint infection of the shoulder is a devastating complication occurring in approximately 1% of cases. The most common organisms responsible for the infection are Cutibacterium acnes (formerly Propionibacterium acnes) (∼39%) and coagulase-negative Staphylococcus (∼29%). Evaluation of patients includes history and physical examination, serologic testing, imaging, possible joint aspiration, and tissue culture. Diagnosing infections caused by lower virulence organisms (eg, C acnes) poses a challenge to the surgeon because traditional diagnostic tests (erythrocyte sedimentation rate, C-reactive protein, and joint aspiration) have a low sensitivity due to the lack of an inflammatory response. Periprosthetic joint infections of the shoulder due to Staphylococcus aureus and other highly virulent organisms are often easy to diagnose and are usually treated with two-stage revisions. However, for infections with C acnes and coagulase-negative Staphylococcus, single- and two-stage revision surgeries have shown similar ability to clear the infection. Unexpected positive cultures for C acnes during revision surgery are not uncommon; the proper management is still under investigation and remains a challenge.