Periprosthetic joint infection (PJI) is one of the most devastating and costly complications following total joint arthroplasty (TJA). Diagnosis and management of PJI is challenging for surgeons. There is no "gold standard" for diagnosis of PJI, making distinction between septic and aseptic failures difficult. Additionally, some of the greatest difficulties and controversies involve choosing the optimal method to treat the infected joint. Currently, there is significant debate as to the ideal treatment strategy for PJI, and this has led to considerable international variation in both surgical and nonsurgical management of PJI. In this review, we will discuss diagnosis and management of PJI following TJA and highlight some recent advances in this field.