Compared with blood, oral fluid has several advantages as a sample for antibody detection. It is simple, safe, painless, and cheap to collect. The only drawback is that while the antibody profiles indicate those in blood, they are at lower concentrations. Antibody capture assays are the method of choice for the detection of microbial antibodies in oral fluid, but their relative lack of sensitivity when based on conventional immunoassay techniques has mostly limited their use to epidemiological applications. Immuno-PCR and time-resolved fluorescence offer more sensitive detection systems that could be applied to oral fluid specimens. We review antibody detection in oral fluid and discuss immuno-PCR and time-resolved fluorescence as candidate systems. Both have the potential to broaden the applications of oral fluid testing to clinical diagnostics.