In spite of great advances in imaging and biochemistry, histological examination of tissues remains a vital part of the multidisciplinary approach to the prevention of the onset, morbidity and mortality of preterm birth. There has been increasing interest in the role of infection and inflammatory cytokines in causation both of early labour and the white matter damage in the brain of preterm infants. However, labour itself is associated with the build up of increased numbers of inflammatory cells in the uterine cervix and increased concentrations of inflammatory cytokines and positive microbiological cultures may reflect carriage or contamination. Confirmation of an infective aetiology in an individual case is best achieved by demonstration of a pathological inflammatory response in tissues, for example, by showing the presence of chorioamnionitis in the placenta. A proper understanding of the poor response to neonatal intensive care of some preterm babies often requires histological examination of the lungs after death, where unsuspected pneumonia, interstitial emphysema and/or pulmonary hypoplasia may help provide an explanation for the adverse outcome in individual cases. The pathophysiological mechanism of brain injury in preterm infants is undergoing re-evaluation, and the systemic study of brain tissue using the latest histological techniques may elucidate the importance of apoptosis in this situation and could point the way towards an effective preventative strategy. Paediatric pathology is also essential to explain many cases of sudden unexpected death in preterm infants, as demonstrated by the recent realisation that death may be caused by total parenteral nutrition fluid-associated myocardial necrosis, and acute cardiac tamponade.