Ureaplasma urealyticum genital tract colonization of pregnant women has been associated with an adverse pregnancy outcome, while its consequent perinatal transmission has been implicated in the development of respiratory disease of the neonate. Clinical manifestations or contributions of ureaplasmal airway colonization in newborns mainly include pneumonia, precocious dysplastic changes and chronic lung disease; although systemic disease has also been documented. This review aims to summarize current diagnostic techniques, pathogenetic mechanisms and pathological data in an attempt to establish an optimal therapeutic approach regarding neonatal U. urealyticum respiratory infection. Related morbidity and mortality, along with the high economic impact of neonatal respiratory disease worldwide, renders this topic particularly interesting and promotes further research in this field.