Biomaterials are used in a variety of medical devices and implants, such as catheters, prosthetic implants and contact lenses. The use of biomaterial implants and medical devices is an increasingly common and often life-saving procedure. However bacterial infections on biomaterials have emerged as a major problem. Implanted devices account for approximately 45% of all hospital-acquired infections and consequently represent a public health issue of major concern. Existing approaches for management of infection involving antibiotic treatment are ineffective for use with implanted devices. Often, the only treatment is surgical intervention by removing the infected device, which leads to high morbidity and mortality. The rapid emergence of bacterial resistance to current antibiotics adds further incentive to the need for development of alternative anti-infective strategies for implanted devices. We have developed a cationic peptide “melimine”, with excellent broad-spectrum antimicrobial activity, that is not cytotoxic at active concentrations and is readily sterilisable. Furthermore, melimine is unusual compared to other AMPs in its ability to retain its activity when covalently attached to surfaces, making it ideal for development as potent antimicrobial coatings and therapies. We have developed methodologies for the covalent attachment of melimine and its analogues on biomaterial surfaces, which demonstrate a broad spectrum of activity against both Gram-negative and Gram-positive bacteria while remaining non-toxic to mammalian cells. In vivo performance of these novel antimicrobial coatings has been evaluated in subcutaneous mouse models. Our results demonstrate that these coatings were able to reduce bacterial colonisation and prevent biofilm formation on surfaces in vitro and reduce the pathogenic potential of a staphylococcal infection in vivo.