INTRODUCTION: Oral squamous cell carcinoma (OSCC) is a significant global health burden. The goals of neoadjuvant chemotherapy (NACT) are to shrink tumors allowing for more conservative surgeries, improve survival and potentially improve quality of life. AREAS COVERED: This review explores the current evidence of utility of NACT in OSCC management. We have covered indications of NACT, types of regimens and their associated toxicities, perioperative challenges with regards to margins and complications. We have also reviewed the upcoming regimens for NACT. EXPERT OPINION: NACT is a potential option for treating borderline resectable and unresectable OSCC. It holds promise for organ preservation (mandibular/tongue). With newer modalities like immunotherapy and targeted therapies, the preferred choice of regimen may evolve. Post NACT, intraoperative margins and choice of adjuvant therapy remain debatable.
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