Vibrio vulnificus infection is the leading cause of death related to seafood consumption in the United States. This virulent, gram-negative bacterium causes two distinct syndromes. The first is an overwhelming primary septicemia caused by consuming raw or undercooked seafood, particularly raw oysters. The second is a necrotizing wound infection acquired when an open wound is exposed to warm seawater with high concentrations of V. vulnificus. Most patients, including those with primary infection, develop sepsis and severe cellulitis with rapid development to ecchymoses and bullae. In severe cases, necrotizing fasciitis can develop. Case-fatality rates are greater than 50 percent for primary septicemia and about 15 percent for wound infections. Treatment of V vulnificus infection includes antibiotics, aggressive wound therapy, and supportive care. Most patients who acquire the infection have at least one predisposing immunocompromising condition. Physician awareness of risk factors for V. vulnificus infection combined with prompt diagnosis and treatment can significantly improve patient outcomes. (Am Fam Physic