Inside the biofilm, antimicrobial agents must overcome high cell density, an increased number of resistant mutants, substance delivery, molecular exchanges, such as high levels of beta-lactamases or inducers of efflux pump expression, and specific adaptive cells, so-called persisters. The environment within the biofilm modulates the response to antibiotics, especially when the SOS response or DNA repair systems are involved. Exposure to subinhibitory concentrations of antibiotics can enhance biofilm formation and mutagenesis. Thus, a global response to cell stress seems to be responsible for antibiotic-induced biofilm formation.