Total joint arthroplasty (TJA) is a surgical procedure, in which parts of damaged joints are removed and replaced with a prosthesis. The main indication of TJA is osteoarthritis, and the volume of TJA is rising annually along with the increase of aged population. Hip and knee are the most common joints, in which TJAs are performed. The TJA prosthesis is composed of metal, plastic, or ceramic device. Even though TJA is the most successful treatment for end-stage osteoarthritis, it is associated with various complications, and periprosthetic joint infection (PJI) is the most serious complication after TJA. With the increasing volume of TJAs, there is a simultaneous rise in the incidence of PJI. Contamination of the surgical wound and the adherence of bacteria to the surface of prosthetic component represent the initial step in the pathogenesis of PJI. The main sources of the contamination are 1) patient's own flora, 2) droplets in the operation room air, and 3) surgical gloves and instruments. Even though modern techniques have markedly reduced the degree of contamination, TJAs cannot be done in completely germ-free conditions and some degree of contamination is inevitable in all surgical procedures. However, not all contamination leads to PJI. It develops when the burden of contamination exceeds the immune threshold or the colony forming units (CFUs) and various factors contribute to a decrease in the CFU level. Surgeons should be aware of the germ burden/CFU concept and should monitor sources of contamination to maintain the germ burden below the CFU to prevent PJI.