In all, 350,000 new cases of oral cancer are reported annually worldwide, 35,000 of these occur in the United States. For decades, the 5-year survival rate has remained low at only 60%, which is mainly due to cancer diagnosis at late and progressed stage. Using saliva as a diagnostic medium could be the key for early detection and thus improved survival rates. Among all salivary constituents, the transcriptome has turned out to be a highly promising biomarker source. So far, seven mRNA and two microRNA markers were found to be discriminatory in saliva of oral cancer patients. This review will give an overview on the field of salivary transcriptome research with focus on oral cancer detection as well as the translation of salivary diagnostics into clinical reality.