In this article, we use the example of head and neck cancer to show how concurrent chemoradiotherapy is used to treat a cancer where locoregional control is central for treatment success. The advent of concurrent chemoradiation has significantly contributed to the curability of head and neck cancer, including locoregionally advanced disease. Preserving organ function and reducing toxic effects are increasingly the focus of clinical trials. We review the available chemoradiotherapy platforms used for head and neck cancer, with initial discussions focused on single-agent cytotoxic-based regimens. We then assess the literature on multiagent-based regimens and include a discussion of the integration of novel agents, such as EGFR inhibitors, and antiangiogenic drugs into treatment platforms. Although single-agent cisplatin-based chemoradiotherapy is still widely used as a standard therapy, we propose that evidence increasingly shows that multiagent-based chemoradiotherapy, and EGFR-inhibitor-based treatments, offer distinct advantages. We provide guidance for clinicians based on current clinical trial evidence on how to choose appropriate treatment platforms for their patients.