Since the 1960s much research has focused on biofilms, i.e. microbial-derived populations irreversibly attached to a surface and embedded in a self-produced polymeric matrix. In this matrix, microbial cells are protected from detrimental external factors such as heat, UV radiation and the host immune system. The most relevant biofilm-related property is the unusual high resistance to antimicrobial therapy, although the origin of this extreme resistance is still the subject of debate. Besides an overview of the main characteristics of biofilms, this review discusses the different resistance mechanisms that lead to increased biofilm-related morbidity and mortality. Adherent communities are involved in at least 65% of all human bacterial infections, particularly in cystic fibrosis and several nosocomial device- related infections. Even in healthy immunocompetent individuals, biofilm infections are rarely resolved and usually persist until the colonized surface is removed from the body. Fundamental research aiming to develop new anti-biofilm strategies will largely depend on the availability of appropriate in vitro models for production and quantification of biofilms. This review describes the most frequently used in vitro biofilm models with respect to the different pitfalls that can emerge from in vitro biofilm research. Despite extensive efforts, no antimicrobial drug has yet been found that completely eradicates adherent microbial populations. The advantages and disadvantages of the currently available therapies are described with a particular focus on antibiotics and biocides. The options and benefits of future antibiofilm therapies are discussed.