Oral cancer survival rates have seen little improvement over the past few decades. This is mainly due to late detection and a lack of reliable markers to predict disease progression in oral potentially malignant disorders (OPMDs). There is a need for highly specific and sensitive screening tools to enable early detection of malignant transformation. Biochemical alterations to tissues occur as an early response to pathological processes; manifesting as modifications to molecular structure, concentration or conformation. Raman spectroscopy is a powerful analytical technique that can probe these biochemical changes and can be exploited for the generation of novel disease-specific biomarkers. Therefore, Raman spectroscopy has the potential as an adjunct tool that can assist in the early diagnosis of oral cancer and the detection of disease progression in OPMDs. This review describes the use of Raman spectroscopy for the diagnosis of oral cancer and OPMDs based on ex vivo and liquid biopsies as well as in vivo applications that show the potential of this powerful tool to progress from benchtop to chairside.