Foot infections are a major cause of morbidity in diabetic patients. Staphylococcus aureus is the most important pathogen in mild infections; moderate to severe infections are frequently polymicrobial. Multidrug resistance is an increasing problem in isolates from diabetic feet. Worldwide, up to 30% of patients with diabetic foot infection (DFI) are colonised with methicillin-resistant S. aureus (MRSA), whilst extended-spectrum beta-lactamase-producing Gram-negative bacteria are also common in some countries. This emergence of drug resistance has coincided with the launch or imminent availability of many new antibiotics. Most of these were developed to target multidrug-resistant Gram-positive bacteria, although some have a spectrum of activity that includes Gram-negative bacteria and anaerobes. There is a variable amount of experience with these agents in treating skin and skin-structure infections (SSSIs), especially for DFI. However, at least some have a spectrum of activity and/or pharmacological properties that suggest that they may be of value in managing DFIs. The aim of this paper is to review evidence for the efficacy of new antibiotics in the management of SSSIs, including any data relating specifically to the diabetic foot, and to consider where they might fit into the therapeutic armory against DFI.