Bacterial infections of the skin range from mild pyodermas to life-threatening necrotizing infections. Pyodermas are most often due to Staphylococcus aureus or beta-hemolytic Streptococcus sp, whereas infections associated with skin ulcers of the extremities, infections following trauma or surgery, and histotoxic necrotizing infections may involve a large number of additional pathogens, including Enterobacteriaceae, Pseudomonas sp, enterococci, and anaerobes. Management of bacterial skin and soft-tissue infections includes appropriate surgical drainage or excision of infected tissue and antimicrobial therapy. The combination of piperacillin and the beta-lactamase inhibitor tazobactam is a newly released antimicrobial, which has excellent in vitro activity against the vast majority of pathogens involved in skin infections. Two multicenter studies recently evaluated the efficacy and safety of piperacillin/tazobactam in the therapy of skin and soft-tissue infections in hospitalized patients. Piperacillin/tazobactam was well tolerated and demonstrated high clinical efficacy for the treatment of these infections.