The emergence of pan-resistant strains of Gram-negative pathogens and the ability of many bacteria to form multidrug-resistant biofilms during chronic infection poses the grave threat of bacterial infections that are truly untreatable with our current armoury of antibiotics. Despite obvious clinical need, few new antibiotics have entered clinical practice in recent years. For 'difficult to treat' Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli, where the presence of outer membrane and multidrug-efflux pumps severely limit the effectiveness of whole classes of antibiotics, the need is particularly pressing. An alternative approach to antimicrobial treatment is to use the well-characterized species-specific colicin-like bacteriocins which are produced by a wide range of Gram-negative bacteria, including Pseudomonas aeruginosa and Escherichia coli. Our current work on colicin-like bacteriocins aims to determine whether these potent antimicrobial agents are effective at killing bacteria growing in the biofilm state and during infection.