The prevention of orthopedic infections is of critical importance to improve patient outcomes and reduce health care costs. Preventative strategies can be employed preoperatively, including mitigation of medical risk factors, methicillin-resistant Staphylococcus aureus decolonization, appropriate skin preparation, and optimizing perioperative antimicrobial prophylaxis; intraoperatively, including utilizing irrigation, topical antibiotics, infection control measures, and timely debridement/optimal surgical techniques; and postoperatively, including consideration of antibiotic duration after primary arthroplasty and reimplantation. This article provides an evidence-based discussion of these strategies while also highlighting areas where ongoing research may be beneficial.