Chemokines have been shown to be important in both inflammation and carcinogenesis and are able to be measured in saliva with relatively robust methods including enzyme-linked immunosorbent assays (ELISA). Thus it has been hypothesized that patients with oral cancer and oral potentially malignant lesions will have elevated levels of specific chemokines in oral fluids and that this may be used as a marker of both the early detection of malignant disease and progression to malignancy. The concept that salivary biomarkers can be easily measured and indicate disease states has profound consequences for clinical practice and may open up new strategies for the diagnosis, prognosis, and potential therapy of oral squamous cell carcinoma (OSCC). This review focuses on our understanding of cytokines and chemokines and the potential role that they may have in clinical practice.