The skin has highly effective mechanical, chemical, and immunologic defenses against microbial invasion. These defenses can be breached, however, when the surface of the skin is broken or when hematologic spread of infection reaches the skin or its underlying tissues. Host factors such as diabetes mellitus may also predispose individuals to skin and soft tissue infections, some of which may threaten limb or life. Management of serious infections of the skin and soft tissue often requires thorough drainage and surgical debridement, as well as aggressive antibiotic therapy. Empiric antibiotic therapy of life-threatening skin structure infections should use an agent effective against a broad range of gram-positive and gram-negative, aerobic, and anaerobic organisms, including producers of beta-lactamase enzymes. The combination of ticarcillin disodium and clavulanate potassium is such an agent, and is safe and effective in the treatment of serious skin and soft tissue infections.