Periprosthetic joint infection (PJI) has moved into the first place as the cause of failure following total knee arthroplasty (TKA). Recent studies have shown that PJI results in higher mortality in patients than many cancers. The economic burden of treating PJI is likely to exceed $1 billion this year in the US. Thus, it is paramount that all efforts are invested to prevent this dreaded complication after total joint arthroplasty (TJA). This article summarizes some of the most effective and proven strategies for prevention of PJI. It is hoped that the article will be of benefit to the readers of the journal.