This chapter discusses the epidemiology, prediction, prevention, and management of spontaneous preterm birth. Preterm birth is usually defined as delivery at any gestation before 37 completed weeks of pregnancy (<37+0 weeks, <259 days). The lower limit of preterm birth and upper limit of late spontaneous miscarriage are blurred as the limit of viability varies with differences in healthcare settings. This condition remains one of the biggest challenges facing obstetricians globally as a result of continuing high rates of morbidity and mortality. Spontaneous preterm birth is caused by a complex collection of pathophysiology with overlapping environmental interactions and behavioural influences that contribute to individual risk. Much debate exists regarding best prevention therapies and there remains a huge need for novel therapies and interventions for both prediction and prevention