Hospital-acquired (nosocomial) infections (HAIs) increase morbidity, mortality and medical costs. In the USA alone, nosocomial infections cause about 1.7 million infections and 99 000 deaths per year. HAIs are spread by numerous routes including surfaces (especially hands), air, water, intravenous routes, oral routes and through surgery. Interventions such as proper hand and surface cleaning, better nutrition, sufficient numbers of nurses, better ventilator management, use of coated urinary and central venous catheters and use of high-efficiency particulate air (HEPA) filters have all been associated with significantly lower nosocomial infection rates. Multiple infection control techniques and strategies simultaneously ('bundling') may offer the best opportunity to reduce the morbidity and mortality toll of HAIs. Most of these infection control strategies will more than pay for themselves by saving the medical costs associated with nosocomial infections. Many non-pharmacological interventions to prevent many HAIs will also reduce the need for long or multiple-drug antibiotic courses for patients. Lower antibiotic drug usage will reduce risk of antibiotic-resistant organisms and should improve efficacy of antibiotics given to patients who do acquire infections.