Periprosthetic infection has always been the most challenging complication after arthroplasty. Although the incidence of this complication has decreased significantly in the last two decades, periprosthetic infection remains the second most common complication after prosthetic loosening after arthroplasty. The literature reports infection rates of 1% to 4% after initial total knee arthroplasty and about 1% after initial total hip arthroplasty. The infection rate after revision surgery is significantly higher, reported to be 3.2% after hip revision and 5.6% after knee revision. The incidence of periprosthetic infections is reported to be increasing again. The treatment of periprosthetic infections is very different from that of aseptic loosening. Therefore, a clear preoperative distinction between periprosthetic infection and aseptic loosening of the prosthesis is essential. However, there is no universally accepted test that can make a definitive diagnosis with absolute accuracy. Therefore, the diagnosis of periprosthetic infection still relies on clinical manifestations and a series of serological and imaging examinations, and intraoperative microbial isolation and culture of periprosthetic tissue remains the ultimate “gold standard” for diagnosis. Serologic tests including sedimentation and C-reactive protein are often used to screen for periprosthetic infections and aseptic loosening after arthroplasty and have a high sensitivity and specificity when combined. However, their sensitivity and specificity vary with the cut-off value selected. Although leukocyte count and percentage neutrophil analysis of joint fluid are frequently used clinically, their role remains unclear; and diagnostic indicators of periprosthetic infection based on joint fluid analysis are currently unclear. The use of imaging or radioisotope methods also has its own limitations. x-ray plain films can provide important information about the cause of joint replacement surgery failure. Infection can lead to imaging changes between the bone and cement or between the bone and prosthesis, including periosteal reaction, osteoporosis, and osteolysis. Rapid and progressive prosthetic loosening without any mechanical cause suggests the possibility of infection. However, there is no significant difference between the imaging presentation of periprosthetic infection and aseptic loosening of the prosthesis. Therefore, radiographs are neither sensitive nor specific for the diagnosis of infection, and their main role is to exclude the etiology of aseptic loosening.