Health care associated infections cause approximately 75,000 deaths annually, in addition to increasing morbidity and costs. Over the past decade, a downward trend in health care associated infections has occurred nationwide. Basic prevention measures include administrative support, educating health care personnel, and hand hygiene and isolation precautions. Prevention of central line or catheter-associated infections begins with avoidance of unnecessary insertion, adherence to aseptic technique when inserting, and device removal when no longer necessary. Specific recommendations for preventing central line associated bloodstream infections include use of chlorhexidine for skin preparation, as a component of dressings, and for daily bathing of patients in intensive care units. Catheter-associated urinary tract infections are the most common device-related health care associated infection. Maintaining a closed drainage system below the patient reduces the risk of infection. To prevent ventilator-associated pneumonia, which is associated with high mortality, mechanically ventilated patients should be placed in the semirecumbent position and receive antiseptic oral care. Prevention of surgical site infections includes hair removal using clippers, glucose control, and preoperative antibiotic prophylaxis. Reducing transmission of Clostridium difficile and multidrug-resistant organisms in the hospital setting begins with hand hygiene and contact precautions. Institutional efforts to reduce unnecessary antibiotic prescribing are also strongly recommended. Reducing rates of methicillin-resistant Staphylococcus aureus infection can be achieved through active surveillance cultures and decolonization therapy with mupirocin. (Copyright (C) 2014 American Academy of Family Physicians.)