Wound sepsis remains perhaps the most feared sequela in the patient who has suffered major burn injuries and leads to overwhelming mortality among patients with extensive burn wounds. The presence of large areas of devitalized, necrotic tissue, coupled with the profound immunosuppression that usually follows major injury, sets the stage for rapid microbial proliferation in the wound; when microbes invade subjacent, previously vi able tissues, invasive burn wound sepsis is defined. Top ical antimicrobial drugs probably have only a limited effect in preventing wound sepsis, and organisms now frequently emerge that are resistant to the commonly used topical agents. Salient factors in the diagnosis and treatment of invasive wound sepsis are discussed in this review. Prevention of wound sepsis, however, is one of the primary objectives of current burn care. Early burn wound excision and immediate wound closure with autograft or a suitable biologic dressing has emerged as the best means for prevention of generalized wound sepsis.