Paper mills are open systems, which provide favorable conditions for microbial growth. Microbial contamination can cause substantial economic losses, including the deterioration of raw materials, interference with production processes by breakdowns and lowering product quality, and eventually, problems in wastewater treatment. Damage is caused by acidification, attack on raw materials, the formation of odorous products, discoloration of pigments, and the formation of methane and hydrogen, thereby producing potentially explosive conditions. Population analyses have revealed that a wide variety of microorganisms are involved, but there appear to be no typical strains associated with paper mills. Current trends in process engineering, such as chlorine-free bleaching, processing at neutral pH, closed cycles, and the use of recycled paper also favor microbial growth and biofilm (slime) formation. A fundamental problem associated with slimes is the extensive matrix of extracellular polymeric substances, which is composed of a large variety of highly hydrated polysaccharides, proteins, nucleic acids, and lipids. No 'silver bullet' against biofouling can be expected, and effective countermeasures have to be based on holistic approaches.