Many antimicrobial agents that target bacteria are cationic and can interact with the anionic lipid components that are exposed on the bacterial membrane. Bacteria vary widely in the nature of the major lipid components that are in the cell membrane. Those bacteria with both anionic as well as zwitterionic or neutral lipids can be induced to form domains in the presence of antimicrobial peptides possessing several cationic charges. This segregation of anionic and zwitterionic lipids into domains can result in the arrest of cell growth or in cell death. Such agents are generally more toxic to Gram-negative bacteria, than to Gram-positive ones. These findings emphasize the importance of the lipid composition of bacterial membranes in determining the susceptibility of the organism to the action of certain antimicrobial agents. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.