Chronic wounds all have bacterial contamination, which will not impair healing. Wound contamination must be distinguished from wound colonization and infection. Bacterial infection in wounds depends on the number of organisms present, their virulence, and host resistance. The most important indicators of infection are both local and systemic host characteristics and a holistic assessment of the patient. Several specimen collection and culture techniques are available to measure bacterial burden in the chronic wound. Advantages and disadvantages of each one discussed along with a rational approach to systemic antibiotic therapy. The presence of foreign material such as skin grafts or skin substitutes may lower the bacterial burden that may impair healing from 1.0 x 10 (6) colony-forming units to 1.0 x 10 (5) or less. The benefits of wound debridement, wound irrigation, and local nonantibiotic modes of treatment have been proven but the use of topical antibiotics and antiseptics requires further assessment. More widespread use of multiple nonantibiotic modalities of treatment for infected chronic wounds and rational antibiotic prescribing should reduce the risk of future antimicrobial resistance such as MRSA.