Saliva and other types of oral samples can readily be used for noninvasive diagnosis of diseases of the oral cavity and systemic diseases. Following an introduction outlining the types of oral samples and the analytes that can be measured in these samples, a detailed description of a novel oral-based diagnostic system to detect multiple bacterial and/or viral pathogens is presented. A reasonably priced, portable, point-of-care diagnostic system should be available within five years.