Skin and soft-tissue infections are among the most common infections encountered by emergency physicians. This article is written from the perspective of the initial evaluation and management of skin and soft-tissue infections in the emergency department. Management pitfalls and clinical dilemmas pertinent to emergency physicians that are not often encountered by infectious disease specialists are highlighted. Special emphasis is placed on the utility of wound and blood cultures, disposition, methicillin-resistant Staphylococcus aureus infections, animal and human bites, and necrotizing skin and soft-tissue infections.