Total joint arthroplasty is one of the most common and most successful orthopaedic procedures. Infection after total joint arthroplasty is a devastating problem that expends patient, surgeon, and hospital resources, and it substantially decreases the chances of a successful patient outcome. Postoperative infection affects approximately 1% to 7% of all total joint arthroplasties, at a cost of approximately $50,000 per infection. Decreasing postoperative periprosthetic joint infection is of the utmost importance for the total joint arthroplasty surgeon. Preoperative, perioperative, intraoperative, and postoperative measures to minimize infection and optimize patient outcomes in total joint arthroplasty are discussed. Preoperative measures include management of patients colonized by Staphylococcus aureus, nutritional optimization, and management of medical comorbidities. Perioperative measures include skin preparation and prophylactic antibiotics. Intraoperative measures include body exhaust suits, laminar flow, ultraviolet light, operating-room traffic control, surgical suite enclosures, anesthesia-related considerations, and antibiotic-loaded bone cement. Postoperative measures include continued antibiotic prophylaxis, blood transfusions, hematoma formation and wound drainage, duration of hospital stay, and antibiotic prophylaxis for future invasive procedures.