Failure of an acute inflammatory response to resolve a wound infection heralds a cascade of events that affects the host and pathogens, culminating in a chronic, refractory condition. The factors contributing to this outcome include immune compromise of the host, antimicrobial resistance, wound-healing deficiencies, and the adherence of pathogens to themselves and wound surfaces via an impenetrable, resistant biofilm. To eradicate chronic infection, the pathogens, biofilm, surfaces available for adherence, and compromised tissue must be removed.