Head and neck cancers remain a significant health problem globally. The addition of chemotherapy to radiotherapy for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) has led to improvements in locoregional disease control and in survival, but is associated with substantial acute and late toxicities. In recurrent and/or metastatic SCCHN, there have been no improvements in survival, despite the manipulation of standard therapeutic regimens and the introduction of newer cytotoxic agents. Over the last decade, targeted therapies have been increasingly used in a range of solid tumor types. This article discusses the clinical evidence for the use of a number of targeted agents in the treatment of locoregionally advanced and recurrent and/or metastatic SCCHN. The article focuses on the epidermal growth factor receptor (EGFR) inhibitors, for which the majority of clinical information is available. These include the monoclonal antibody (MAb) cetuximab and the tyrosine kinase inhibitors, erlotinib and gefitinib. Clinical data for the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, are also presented.