Antimicrobial selection for prophylaxis in surgery is based on the site of surgery, likely pathogen involved in addition to the in vitro efficacy, pharmacokinetics and the cost of the drugs used. For example, prophylactic agent in cardiovascular or orthopedic and skin and soft tissue surgery must cover against Staphylococcus aureus as well as the enterobacteriaceae; cephalosporins being adequate. On the other hand, any drug used in cases of urologic surgery must be excreted by the kidney in an active state and should also be active against E. coli, a common uropathogen such as any cephalosporins or penicillin. Drugs like macrolides and tetracyclines accumulate in the prostate and are good for prostate surgery by they are not excreted well by the kidney and therefore useless for urological prophylaxis. It is important to note that even treating minor infections in a neurosurgical patient, we must use an antibiotic that cross blood-brain barrier otherwise meningitis might develop. In cases of gastrointestinal tract, surgery on the colon and appendix requires special coverage against anaerobic bacteria especially Bacteroides fragilis. On the other hand surgery on the stomach, gall-bladder and upper two thirds of small intestine, it is adequate to use drugs to cover aerobic bacteria such as E. coli. Most studies show that a single most effective antibiotic is enough and it is unnecessary to use two or more drug combinations.