The burn wound represents a susceptible site for opportunistic colonization by organisms of endogenous and exogenous origin. Patient factors such as age, extent of injury, and depth of burn in combination with microbial factors such as type and number of organisms, enzyme and toxin production, and motility determine the likelihood of invasive burn wound infection. Burn wound infections can be classified on the basis of the causative organism, the depth of invasion, and the tissue response. Diagnostic procedures and therapy must be based on an understanding of the pathophysiology of the burn wound and the pathogenesis of the various forms of burn wound infection. The time-related changes in the predominant flora of the burn wound from gram-positive to gram-negative recapitulate the history of burn wound infection. Proper clinical and culture surveillance of the burn wound permits early diagnosis of gram-positive cellulitis, and the stable susceptibility of beta-hemolytic streptococci to penicillin has eliminated the threat of this once common burn wound pathogen. Selection and dissemination of intrinsic and acquired resistance mechanisms increase the probability of burn wound colonization by resistant species such as Pseudomonas aeruginosa. Even so, effective topical antimicrobial chemotherapy and early burn wound excision have significantly reduced the overall occurrence of invasive burn wound infections. Individual patients, usually those with extensive burns in whom wound closure is difficult to achieve, may still develop a variety of bacterial and nonbacterial burn wound infections. Consequently, the entirety of the burn wound must be examined on a daily basis by the attending surgeon. Any change in wound appearance, with or without associated clinical changes, should be evaluated by biopsy. Quantitative cultures of the biopsy sample may identify predominant organisms but are not useful for making the diagnosis of invasive burn wound infection. Histologic examination of the biopsy specimen, which permits staging the invasive process, is the only reliable means of differentiating wound colonization from invasive infection. Identification of the histologic changes characteristic of bacterial, fungal, and viral infections facilitates the selection of appropriate therapy. A diagnosis of invasive burn wound infection necessitates change of both local and systemic therapy and, in the case of bacterial and fungal infections, prompt surgical removal of the infected tissue. Even after the wounds of extensively burned patients have healed or been grafted, burn wound impetigo, commonly caused by Staphylococcus aureus, may occur in the form of multifocal, small superficial abscesses that require surgical debridement. Current techniques of burn wound care have significantly reduced the incidence of invasive burn wound infection, altered the organisms causing the infections that do occur, increased the interval between injury and the onset of infection, reduced the mortality associated with infection, decreased the overall incidence of infection in burn patients, and increased burn patient survival.