Antimicrobial resistance has emerged as an important determinant of outcome for patients in the intensive care unit (ICU). This is largely due to the administration of inadequate antimicrobial treatment, which is most often related to bacterial antibiotic resistance. In addition, the escalating problem of antimicrobial resistance has substantially increased overall health care costs. This increase is a result of prolonged hospitalizations and convalescence associated with antibiotic treatment failures, the need to develop new antimicrobial agents, and the implementation of broader infection control and public health interventions aimed at curbing the spread of antibiotic-resistant pathogens. Intensive care units are unique because they house seriously ill patients in confined environments where antibiotic use is extremely common. They have been focal points for the emergence and spread of antibiotic-resistant pathogens. Effective strategies for the prevention of antimicrobial resistance in ICUs have focused on limiting the unnecessary use of antibiotics and increasing compliance with infection control practices. Clinicians caring for critically ill patients should consider antimicrobial resistance as part of their routine treatment plans. Careful, focused attention to this problem at the local ICU level, using a multidisciplinary approach, will have the greatest likelihood of limiting the development and dissemination of antibiotic-resistant infections.