Saliva as a diagnostic fluid enables non-invasive sampling, which can be performed even by an untrained person. Saliva is, thus, particularly useful for large population screenings, for children, elderly and whenever repeated samplings are needed. Saliva is a plasma filtrate actively modified by the salivary glands. Saliva could replace some routine blood tests in the future. The sources of salivary RNA include oral epithelial cells and oral micro-organisms. Recent developments suggest that using known salivary RNA markers, it is possible to diagnose diseases such as oral carcinoma and other diseases will be added soon. Salivary RNA can be used to identify oral bacteria and to determine the expression of specific genes. On a systemic level, it provides information about the whole oral transcriptome and microbiome. Despite the small amount of salivary RNA, the issues with its isolation have been overcome. Saliva, thus, contains RNA of sufficient quality and quantity for sensitive and specific analyses. Salivary RNA can provide medically relevant information about oral microbiome, oral carcinoma, but also breast and pancreatic cancer and is, thus, a promising tool for future research and clinical diagnostics.