Systematic reviews and meta-analyses published in recent years have allowed drafting of evidence-based guidelines for antibiotic prophylaxis in orthopedic and trauma surgery. It is important to recognize the limitations of the recommendations derived from the available body of evidence. Since some of the most relevant randomized controlled clinical trials were performed more than 20 years ago, it is sometimes difficult to apply the data to today's clinical practice. In establishing consensus guidelines, it could prove difficult to identify areas for improvement through further research and better compliance. Although recommendations for optimized treatment of orthopedic implant infections are not currently based on first-class evidence, there are very promising new concepts emerging in this field, and we are awaiting more data and decisive conclusions from larger clinical trials.