Antimicrobial prophylaxis is widely performed in any surgical procedures to prevent postoperative infections. However, we have neither double-blind placebo-controlled studies nor sufficient surveillance of postoperative infections that are common in Europe and the United States, and therefore there is little convincing scientific basis accounting for the validity of this therapy. In addition, prophylactic agent is still uncovered by medical insurance despite the persistent arguments as to its necessity. To establish the guidelines in our own country, a greater deal of evidence needs to be accumulated. Strategies for antimicrobial prophylaxis should be determined based on the types of possible postoperative infections and the classifications of operations according to contamination levels in individual operative fields. This process may involve the precise selection of prophylactic agents for suspected contaminating bacterial species in each operative organ and their administration regimens suitable for the individual surgery. Upon selection of prophylactic agents for postoperative infections, various conditions should be considered: e.g., susceptibility, resistance, blood concentrations, urinary excretion, transition into body fluid and tissues, and adverse reactions. The first and second generations of cephem and cephamycin derivatives can be the first choice, but the use of various other antibacterial agents may be necessary for resistant bacterial strains such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). Cyclic therapy based on penicillins (including mixtures), cephems (including cephamycins) and phosphomycins also seems useful for such resistant strains. At present, there is only limited evidence supporting the importance of prophylactic agents. Controlled trials employing well-designed protocols that endure scientific criticism must be done with due consideration for medical economics.