New developments in antimicrobial therapy encompass both the investigation of new pharmacological agents and new uses for available antibiotics. The clinical spectrum must always be taken into account when using antibiotics. The patient may not fit the typical age or characteristic for a given infectious condition, or may be immunocompromised and require a higher index of suspicion in order to receive adequate evaluation and therapy. This review encompasses several of the more recent developments that affect the diagnosis and treatment of skin, soft tissue, and osseus infections.