To gain a deeper knowledge of the very complexinteraction of antimicrobial peptides with bacteria, simplified models consisting of short cationic peptides and bilayer membranes with distinct lipid composition were studied. The scope of this work is a systematic determination of the driving forces for the interaction of short cationic model peptides with lipid bilayers and monolayers. The lipid-peptide interaction is a subtle interplay of electrostatic and hydrophobic interactions.The geometry determined by the peptide sequence, its secondary structure, and the lipid headgroup distance plays a role. The peptide secondary structure is more important and the three different parameters of hydrophobicity, charge distance, and charge localization are the key elements determining the binding affinity. The lipid component also influences the interaction with the model peptides. With the help of this work, abetter understanding of the relationship between function and structure of antimicrobial peptidesis gained.