In the last three decades, more work has been done on apoptosis and its role in the pathogenesis of many diseases including cancer. In almost all instances of cancer, dysregulation of cell death (apoptosis) and cell proliferation have been found to play a major role in tumourigenesis. A lot of progress has been made on understanding the molecular basis of apoptosis and its regulatory mechanisms. This review focuses on current knowledge on the regulation of apoptosis in oral squamous cell carcinoma, current methodologies and methodological consideration in estimation of cell death in tissue sections and the clinical significance of apoptosis related molecules in progression of oral squamous cell carcinoma.