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Deep periprosthetic infection after total knee arthroplasty is a serious and challenging complication for the orthopedic surgeon. Muscular flaps may represent a valid treatment option for the treatment of this condition. We present a systematic literature review about the use of muscular flaps for the treatment of knee prosthetic joint infection. The review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 70 articles, out of 589 titles, were considered eligible for the full-text analysis. Finally, 27 studies that met inclusion criteria were included in this review. Overall, 345 patients (139 males, 206 females) suffering from TKA infection treated with muscular flaps were collected. The mean age was 57.3 years. Mean follow-up, reported in all studies, was 30.1 months. The results presented by the different authors, highlight the effectiveness of muscular flaps for the treatment of periprosthetic infection, in terms of function, limb salvage, prevention of recurrences, cost-effectiveness, and quality of life postoperatively. Muscle flaps provide an excellent management option for patients with persistent infection after total knee arthroplasty.