Periprosthetic joint infection (PJI) is a major complication of arthroplasty and poses challenges to surgeons. This is associated with several grave complications, functional loss, and even mortality. Choosing an efficient management protocol for modern diagnostic techniques and treatment for eradicating pathogens is viable for many individuals. In this chapter, we will discuss the current knowledge of the diagnosis, prevention, and treatment of the PJI of the lower limb.