In the present review, the authors focus on skin and soft tissue infections (SSTIs), a set of commonly observed pathologies which can present different features in terms of site and localization, clinical characteristics, and the aetiological agent responsible; their severity is related to the depth of the affected sites. After a brief introduction to the diverse classification criteria which are currently adopted by various authors, the aetiology and role of the most frequently occurring pathogen, Staphylococcus aureus, often methicillin-resistant is discussed, as well as the possible therapeutic options. We first present the internationally recommended guidelines, and stress that SSTI management has to conform to different criteria, in accordance with the different clinical settings: mild infections require simple and cost-saving treatments while severe infections make timely and aggressive treatments mandatory. The review then reports the recent data concerning the efficacy of new antimicrobials for treating SSTIs. In particular, results observed with linezolid, tigecycline, and daptomycin are discussed.