The prediction of preterm birth may be important (1) to initiate risk specific treatment; (2) to define a population that is at risk in which to study a particular treatment; or (3) to better understand the pathways that lead to preterm birth. Biologic fluids that have been used as sources for tests include serum, plasma, amniotic fluid, urine, vaginal and cervical secretions, saliva, and even periodontal fluid. We discuss the types of substances that are found in body fluids (eg, organisms, cytokines, enzymes, hormones) that have been studied as predictors of preterm birth, the fluids in which they are found, and issues that are related to the timing of the test, the cost, and the ease of fluid collection and processing. We emphasize that a test for any of these substances should not be introduced into clinical practice until the use of the test, which is followed by an appropriate intervention, leads to a reduction in preterm birth.