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Chronic infections affect 17 million people yearly, and approximately 550,000 people die each year from, or with, their chronic infections. Acute and chornic infection differences are well known to clinicians, but the role of bacteria in producing these clinical differences remains poorly understood.This review relies on basic science, clinical studies, and a general review of the medical biofilm literature. The basic science studies are level A and B quality of evidence. The clinical studies are mainly retrospective cohort (level B) and case studies (level C). The biofilm literature includes reviews with varying levels of evidence. All articles have been peer reviewed and meet the standard of evidence-based medicine.Acute infections are associated with planktonic bacteria and must be diagnosed rapidly and accurately to prevent tissue damage and/or death. In contrast, biofilm behavior pursues a more parasitic course by producing sustained host hyperinflammation, with the biofilm feeding on plasma exudate. Chronic infections vacillate over long periods of time, responding only partially to antibiotics and reemerging once the antibiotics are withdrawn. Chronic wounds exhibit similar clinical behavior seen in other chronic infections and are associated with biofilm phenotype bacteria on their surface. Biofilm infections, such as chronic wounds, cannot be adequately diagnosed with current clinical cultures; therefore, molecular methods are necessary.Biofilm phenotype bacteria require multiple concurrent strategies, including débridement and targeted antibiofilm agents. Biofilm phenotype bacteria predominate on the surface of wounds, and biofilm-based management improves wound healing outcomes, indicating that biofilm is the right target for managing the bioburden barrier of chronic wounds.