INTRODUCTION: Oralsquamous cell carcinoma (OSCC) is a significant global health burden. The goals ofneoadjuvant chemotherapy (NACT) are to shrink tumors allowing for moreconservative surgeries, improve survival and potentially improve quality oflife. AREASCOVERED: Thisreview explores the current evidence of utility of NACT in OSCC management. Wehave covered indications of NACT, type of regimens and their associatedtoxicities, perioperative challenges with regards to margins and complications.We have also reviewed the upcoming regimens for NACT. EXPERTOPINION: NACT isa potential option for treating borderline resectable and unresectable OSCC. Itholds promise for organ preservation (mandibular/tongue). With newer modalitieslike immunotherapy and targeted therapies, the preferred choice of regimen mayevolve. Post NACT, intraoperative margins and choice of adjuvant therapy remaindebatable.