One of the global challenges of the 21st century is the increase in mortality from infectious diseases against the backdrop of the spread of antibiotic-resistant pathogenic microorganisms. In this regard, it is worth targeting antibacterials towards the membranes of pathogens that are quite conservative and not amenable to elimination. This review is an attempt to critically analyze the possibilities of targeting antimicrobial agents towards enzymes involved in pathogen lipid biosynthesis or towards bacterial, fungal, and viral lipid membranes, to increase the permeability via pore formation and to modulate the membranes' properties in a manner that makes them incompatible with the pathogen's life cycle. This review discusses the advantages and disadvantages of each approach in the search for highly effective but nontoxic antimicrobial agents. Examples of compounds with a proven molecular mechanism of action are presented, and the types of the most promising pharmacophores for further research and the improvement of the characteristics of antibiotics are discussed. The strategies that pathogens use for survival in terms of modulating the lipid composition and physical properties of the membrane, achieving a balance between resistance to antibiotics and the ability to facilitate all necessary transport and signaling processes, are also considered.