Early detection is very crucial for successful management of oral cancer or any disease as such. Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of malignancy of oral cavity. In the field of cancer research, there is always an ongoing quest for newer methods to lower the morbidity and mortality associated with OSCC. Saliva, a readily available noninvasive biofluid with constant contact with oral cancer lesion, offers an appealing alternative to serum and tissue testing. This review throws light on incorporation of newer technologies for harnessing the saliva to its fullest potential with increased specificity and sensitivity toward identification of cancer-specific molecular signatures for the development of point-of-care applications that could be used at the clinical setting.