Bacterial biofilm resistance is a very serious problem of modern medicine and industry practice. Microorganisms forming biofilm initiate multilevel resistance mechanisms that protect cells against antibacterial substances. This resistance is higher than antibiotics and disinfectants tolerance of planktonic bacteria. Ineffective of antibacterial compounds action on biofilm depends on biofilm structure, slowing down the antibiotics diffusion speed, environmental factors in which biofilm is formed, the presence of capsule of bacteria and the activity of 'efflux pumps' proteins. The process of signal molecules formation by bacteria and releasing them to the medium is also very relevant aspect. In this paper, the changes in the molecular level that induces bacterial biofilm resistance against antimicrobial agents are also described.