At any given time, 25 to 35 percent of hospitalized patients are receiving systemic antibiotics (Eickhoff, 1991) to treat active infections or to prevent potential infections. The heavy use of antibiotics in the hospital exerts enormous selective pressure for the emergence and spread of antibioticresistant bacteria. Consequently, many of the two million bacterial infections acquired in the hospital are antibiotic-resistant, and a few are resistant to every antibiotic currently approved for use. Some hospitals have reduced infections from antibiotic-resistant bacteria through a combination of infection control procedures that prevent the spread of the resistant organisms and through monitoring and control of antibiotic use. This chapter 1) describes antibiotic use in hospitals and its contribution to the rise of antibioticresistant nosocomial infections, 2) discusses current efforts to control antibiotic-resistant infections, 3) explores medical and financial factors that make such efforts difficult to implement in hospitals, and 4) discusses some possible solutions.