Biofilms are ubiquitous and medically important complex structures consisting of microbial-associated cells embedded in self-produced extracellular matrix of hydrated extrapolymeric substances, which are irreversibly attached to a biological or nonbiological surface. Bacteria that reside as biofilms are resistant to traditional therapy. This alternative community in which microbes exist has recently attracted interest as a potential reason why chronic wounds do not heal. This may be especially important for diabetic foot ulcers, which are often characterized by their refractory nature, their predisposition to have associated underlying infection, and their improvement with débridement. Animal and in vitro models have been developed to better study biofilms, which will allow a venue for therapeutic intervention. Potential opportunities exist that include prevention of bacterial attachment, prevention of biofilm formation, disruption of the biofilm to allow penetration of topical antimicrobial agents, interference with quorum sensing, and enhancement of bacteria dispersion from biofilms to a more easily destroyed planktonic state.