The term oral cavity cancer (OSCC) constitutes cancers of the mucosal surfaces of the lips, floor of mouth, oral tongue, buccal mucosa, lower and upper gingiva, hard palate and retromolar trigone. Treatment approaches for OSCC include single management with surgery, radiotherapy [external beam radiotherapy (EBRT) and/or brachy therapy], as well as adjuvant systemic therapy (chemotherapy and/or target agents); various combinations of these modalities may also be used depending on the disease presentation and pathological findings. The selection of sole or combined modality is based on various considerations that include disease control probability, the anticipated functional and cosmetic outcomes, tumor resectability, patient general condition, and availability of resources and expertise. For resectable OSCC, the mainstay of treatment is surgery, though same practitioners may advocate for the use of radiotherapy alone in selected "early" disease presentations or combined with chemotherapy in more locally advanced stage disease. In general, the latter is more commonly reserved for cases where surgery may be problematic. Thus, primary radiotherapy ± chemotherapy is usually reserved for patients unable to tolerate or who are otherwise unsuited for surgery. On the other hand, brachytherapy may be considered as a sole modality for early small primary tumor. It also has a role as an adjuvant to surgery in the setting of inadequate pathologically assessed resection margins, as does postoperative external beam radiotherapy ± chemotherapy, which is usually reserved for those with unfavorable pathological features. Brachytherapy can also be especially useful in the reirradiation setting for persistent or recurrent disease or for a second primary arising within a previous radiation field. Biological agents targeting the epithelial growth factor receptor (EGFR) have emerged as a potential modality in combination with radiotherapy or chemoradiotherpy and are currently under evaluation in clinical trials.