A great number of biologically active peptides interact with phospholipid membranes. Antimicrobial peptides are among these peptides and for a long time it was believed that interaction with microbial membranes was the main, if not the only, cause for their microbicidal activity. In recent years, based on new experimental evidence, there has been serious doubts about this hypothesis. Antimicrobial peptides, as charged and/or hydrophobic molecules, can interact with targets other than lipid membranes. These interactions could be essential for their mechanism of action. It is now evident that the mechanism of the antimicrobial function of small, natural or synthetic, peptides has a complex nature and needs to be re-investigated on the basis of new findings. However, biophysical properties of these peptides in solution, at membrane interface, and in membrane interior are essential for understanding the complex mechanism of their antibiotic activity. The focus of this brief review will be on the conformation and thermodynamics of two groups of cationic linear and cyclic antimicrobial peptides in their interaction with lipid membranes. The biophysical properties of these antimicrobial peptides have been studied in the past several years in our laboratory. In addition to their cationic properties, another common feature of these peptides is the presence of aromatic amino acids in their primary structures. Both groups of peptides interact with membrane surfaces, and their mode of interaction is dependent on their conformation in solution, their amino acid composition, as well as the lipid composition of membranes.