During the past decade considerable evidence, first based on individual case reports and later on prospective studies, has indicated that Ureaplasma urealyticum may be an important neonatal pathogen. Infections of the bloodstream, respiratory tract, and central nervous system have been documented. Isolation of U. urealyticum from the lower genital tract in a large percentage of healthy women and the likelihood that many may transmit infection to their offspring, either in utero or at delivery, have made it difficult to determine the pathogenic potential of this organism in perinatal infections. Early studies showed that newborn infants colonized superficially by U. urealyticum suffered no adverse effects. However, more recent studies involving primarily preterm neonates have clearly demonstrated the ability of U. urealyticum to produce invasive disease. Future investigation should be directed towards a more in-depth characterization of the basic biology of U. urealyticum, identification of the risk factors predictive of invasive disease among those colonized, and the development of rapid tests to detect its presence and to determine the overall significance and prevalence of this organism in specific neonatal infections. © 1993, by The University of Chicago.