Periprosthetic joint infection is a feared complication after the megaprosthetic reconstruction of oncologic and non-oncologic bone defects of including the knee or hip joint. Due to the relative rarity of these procedures, however, optimal management is debatable. Considering the expanding use of megaprostheses in revision arthroplasty and the high revision burden in orthopedic oncology, the risk of PJI is likely to increase over the coming years. In this non-systematic review article, we present and discuss current management options and the associated results focusing on studies from the last 15 years and studies from dedicated centers or study groups. The indication, surgical details and results in controlling infection are presented for debridement, antibiotics, irrigation and retention (DAIR) procedure with an exchange of the modular components, single-stage implant exchange, two-stage exchanges and ablative procedures.