Prophylactic antibiotic treatment is mandatory in every operation involving an orthopedic implant. Carefully selected and correctly administered antibiotics can provide effective protection of the implant from bacterial colonization. The prevention of deep wound infection in joint replacement includes several procedures and measures which constitute three basic groups: 1) Promotion of patient's ability to resist infection (careful pre-operative preparation, elimination of potential infectious loci, good nutritional status, etc). 2) Optimal conditions for the operative wound (surgical technique, prophylactic antibiotics). 3) Reduction of the number of bacteria brought in the wound (control measures, super-sterile operating theatres). Clear rules for the system of prophylactic antibiotic treatment should be adopted. A program in which responsibility for antibiotic administration was shifted from the nursing staff to the anesthesiologist in the operating theatre showed improved outcomes and reduced costs. Poor timing of prophylactic antibiotic administration is one of the basic mistakes. If the wound happened to be contaminated during surgery, the first three post-operative hours would be most decisive for the development of infection. An effective bactericidal concentration of antibiotic should be present in tissues and serum immediately after surgery has begun. Therefore the appropriate time for antibiotic application is before a skin incision is made, and not after the operation has started; the highest serum and bone tissue levels appear 20 to 30 min. after intravenous antibiotic injection. To allow antibiotics to reach target tissues, they should be introduced at least 10 min. before tourniquet application. For long surgical procedures or when blood loss is high, an additional dose of antibiotics is recommended during the operation. If a sample for bacterial cultivation is required, antibiotic administration is postponed until during surgery. However, this is used only in indicated cases when deep infection is suspected and no assessment of the causative agent is available. Otherwise this approach carries a high risk of infectious complications in aseptic revision arthroplasty. Long-term, unjustified administration of antibiotics leads to an increase in resistance to the antibiotic involved. Some studies show that a day's course is as effective as a seven-day one. A shorter antibiotic course decreases the costs, reduces side-effects and minimizes the development of resistance. An optimal duration of antibiotic treatment has not been defined yet, and is still a hot issue for discussion. Many authors recommend one pre-operative antibiotic dose and, according to the kind of antibiotic, agree to its 24-hour administration in order to lower the toxic effect of antibiotic and to prevent selection of resistant microorganisms. The choice of suitable antibiotics for prophylactic treatment should be based on the range of agents causing joint replacement infections and the pharmacological properties of the drug. This should have minimal toxicity, should be well tolerated by the patient and, from the epidemiological point of view, should have a low risk of inducing resistance because of frequent use. Naturally, it is not possible to include all antibiotics against all causative agents and therefore attention should be paid, in the first place, to Gram-positive bacteria, i. e., staphylococci and streptococci, which are the most common causes of infectious complications associated with joint replacement. Because of difficulties related to the right choice of antibiotic, it is recommended to keep a record of complications in each patient in order to provide feedback and to facilitate the establishment of reliable antibiotic-based prevention. The prevention of infection in orthopedics is a comprehensive issue. It cannot be expected that prophylactic antibiotic treatment will compensate for mistakes made in operative protocols, for inadequate operative techniques, for shortcomings in operating theatre equipment or insufficient preparation of patients.