Each day, humans produce approximately 0.5 through 1.5 liters of saliva, a biofluid that is rich in biological omic constituents. Our lack of understanding how omic biomarkers migrate from diseased tissue to the saliva has impeded the clinical translation of saliva testing. Although such biomarkers must be conveyed via the vascular and lymphatic systems to the salivary glands, the molecular mechanisms that underlie this transport remain unclear. Although COVID-19 highlighted the need for rapid and reliable testing for infectious diseases, it represents only one of the many health conditions that potentially can be diagnosed using a saliva sample.The authors discuss salivaomics, saliva exosomics, and the mechanisms on which saliva diagnostics are based and introduce a novel electrochemical sensing technology that may be exploited for saliva liquid biopsy.The utility of saliva for screening for lung cancer is under investigation. Saliva testing may be used to stratify patients, monitor treatment response, and detect disease recurrence. The authors also highlight the landscapes of saliva-based SARS-CoV-2 testing and ultrashort cell-free DNA and outline how these fields are likely to evolve in the near future.Breakthroughs in the study of saliva research, therefore, will facilitate clinical deployment of saliva-based testing.