Antimicrobial peptides (AMPs) are integral components of the innate immune defence system of all complex organisms including plants, insects, and mammals. They have wide range of antibacterial, antifungal, antiviral, and even anticancer activities, therefore AMPs are attractive candidates for developing novel therapeutic approaches. Cationic α-helical membrane disrupting peptides are perhaps the most widely studied subclass of AMPs due to their common fundamental characteristics that allow for detailed structure-function analysis and therefore offer a promising solution to the threat of multidrug resistant strains of bacteria. The majority of the studies of AMP activity focused on the biological and biophysical aspects of membrane disruption; the understanding of the molecular mechanism of action from the physicochemical point of view forms a relatively small subfield. This review will provide an overview of these works, focusing on the empirical and thermodynamic models of AMP action.