Device-associated infections are responsible for about half of nosocomial infections and can cause major medical and economical sequelae. Despite adherence to basic infection control measures, which constitute the mainstay for preventing infection, infections associated with certain devices continue to exist at unacceptably high rates. Potentially-preventive, antimicrobial-utilizing strategies include systemic antibiotic prophylaxis and local administration of antimicrobial agents (antibiotics or antiseptics), which includes antimicrobial irrigation of the surgical field, placement of antimicrobial carriers, antiseptic cleansing of the skin, dipping of surgical implants in antimicrobial solutions, and inserting antimicrobial-coated implants. Since bacterial colonization of the indwelling device is a prelude to infection, prevention of device colonization may lead to a lower rate of clinical infection. Different approaches for antimicrobial coating of devices have been variably successful in preventing device-associated infections. Optimal characteristics of antimicrobial coating can help predict the likelihood and degree of clinical protection against infection. This review addresses the impact of device-related infection, antimicrobial-utilizing approaches for preventing infection, clinical protection afforded by different types of antimicrobial coating, characteristics that predict the ability of antimicrobial coating of devices to prevent clinical infection, and future directions of antimicrobial coating.