Preterm birth is a leading cause of neonatal and childhood mortality worldwide. Advances in medical technologies and therapeutic perinatal and neonatal care have substantially improved the rates of survival among preterm infants, even at the lowest gestational ages. However, the functional and structural immaturity of preterm infants’ organs and systems is responsible for the development of multiple short- and long-term complications, which significantly contribute to the healthcare and socioeconomic burden of preterm birth. Among these complications, the most common include respiratory distress, bronchopulmonary dysplasia, persistent patency of the ductus arteriosus, necrotizing enterocolitis, brain injury, poor nutrition and growth, and sensorineural deficits. In turn, these conditions variously contribute to the development of adverse neurocognitive outcomes, with relevant long-term implications. This chapter aims to review the main risk factors associated with preterm birth, the clinical features of preterm infants, and the most frequent complications encountered in this frail population, highlighting the importance of a multidisciplinary approach and a long-term neurodevelopmental follow-up