Infection is defined as a homeostatic imbalance between the host tissue and the presence of microorganisms. It is associated with a large variety of wound occurrences ranging from traumatic skin tears and burns to chronic ulcers and complications following surgery and device implantations. If the wound setting manages to overcome the microorganism invasion by a sufficient immune response then the wound should heal. If not, the formation of an infection can seriously limit the wound healing process. Evidence of increasing bacterial resistance is on the rise, and complications associated with infections are therefore expected to increase. The main goal in treating various types of wound infections is to decrease the bacterial load in the wound to a level that enables wound healing processes to take place. Conventional systemic delivery of antibiotics entails poor penetration into ischemic and necrotic tissue and can cause systemic toxicity with associated renal and liver complications, which result in a need for hospitalization for monitoring. Alternative local delivery of antibiotics by either topical administration or by a delivery device may enable the maintenance of a high local antibiotic concentration for an extended duration of release without exceeding systemic toxicity. The present review describes approaches for local prevention of bacterial infections based on antibiotic-eluting medical devices. These devices include bone cements, fillers and coatings for orthopedic applications, wound dressings based on synthetic and natural polymers, intravascular devices, vascular grafts and periodontal devices. Part of the review is dedicated to our novel composite drug-eluting fibers and structured drug-eluting films, which are designed to be used as basic elements of various devices. In this review emphasis is placed on processing techniques, microstructure, drug release profiles, biocompatibility and other relevant aspects necessary for advancing the therapeutic field of antibiotic-eluting devices.