Over the past 50 years, increased interest in the discipline of surgical infection has resulted in advances in post-surgical infection control. Early investigations focused on the importance of anaerobic microflora to postoperative infection and paved the way for significant improvements in prophylactic and therapeutic antibiotic treatment of surgical patients. Later research centered on the identification of risk factors to better predict postoperative infection rates. This article reviews the evolution of postoperative infection control and highlights antibiotic prophylaxis in specific clinical situations.