This presentation will discuss fundamental physical, chemical, and biological concepts important to understanding control of detrimental biofilms such as those that can foul and contaminate food processing equipment. Three phenomena that are important in the action of antimicrobial agents against a biofilm will be examined: diffusion, hydrodynamics, and physiology. The penetration of a biocide into a biofilm is governed by the balance of reaction and diffusion. Oxidizing agents in particular are subject to retarded or incomplete penetration due to their inactivation within the biofilm. Oxygen and nutrient concentration gradients within biofilms lead to stratified patterns of anabolic activity. For example, microelectrode technology demonstrates the presence of anoxic niches in biofilms exposed to aerated medium. Staining techniques reveal that the same biofilm can harbor, in distinct spatial niches, growing and dormant cells. Variation in the physiological activity is accompanied by alterations in susceptibility to antimicrobials. Time-lapse imaging of biofilms subjected to antimicrobial treatments reveals that in many cases these treatments do not remove the biofilm. In instances where removal is observed it is clear that forces applied by the flowing fluid are an important component of the removal process. The biofilm defense against biocides and antibiotic is multifactorial and so requires integrated and interdisciplinary science.