Bone and joint infections are difficult to treat, and increasing antibiotic resistance has only made them more challenging. This has led to renewed interest in phage therapy (PT). The aim of this systematic review was to determine success rate, current treatment modalities and safety of PT in bone and joint infections. A systematic search of PubMed, EMBASE and Cochrane databases as well as the journal PHAGE for literature published between January 2000 and April 2021 was conducted according to PRISMA guidelines to identify all human studies assessing bacteriophages as therapy for bone and joint infections. All study designs and patient populations were eligible. The review’s primary outcome was success rate. Twenty records describing a total of 51 patients and 52 treatment episodes were included. No randomized controlled studies were identified. The overall success rate was 71% (n = 37/52). Topical administration alone was the most frequent administration route (85%, n = 44/52). Antibiotics were administered concomitantly with PT in the majority of treatments (79%, n = 41/52), and surgery was performed for 87% (n = 45/52) of treatment episodes. Four minor adverse events related to PT were reported, representing 8% (n = 4/52) of treatment episodes. PT for bone and joint infections has not been evaluated in any randomized controlled clinical study, and current administration modalities are highly variable between case reports and case series. While publications included here show potential benefit and few adverse effects, clinical trials are warranted to assess the efficacy of PT for bone and joint infections and determine optimal treatment modalities. Cite this article: EFORT Open Rev 2021;6:1148-1156. DOI: 10.1302/2058-5241.6.210073