Head and neck squamous cell carcinoma (HNSCC) is one of the world top ten most common cancers withits highest occurrence in the Indian subcontinent and different aggressive and etiological behavioural patterns.The scenario is only getting worst with the 5 year survival rates dropping to 50%, persistent treatment failuresand frequent cases of relapse/recurrence. One of the major reasons for these failures is the presence of cancerstem cells (CSCs), a small population of cancer cells that are highly tumourigenic, capable of self-renewal andhave the ability to differentiate into cells that constitute the bulk of tumours. Notably, recent evidence suggeststhat cancer stem cells are especially resistant to conventional therapy and are the “drivers” of local recurrenceand metastatic spread. Specific markers for this population have been investigated in HNSCC in the hope ofdeveloping a deeper understanding of their role in oral cancer pathogenesis, elucidating novel biomarkers forearly diagnosis and newer therapeutic strategies. This review covers the fundamental relevance of almost all theCSC biomarkers established to date with a special emphasis on their impact in the process of oral tumourigenesisand their potential role in improving the diagnosis, prognosis and treatment of OSCC patients.