Preterm birth, defined as delivery before 37 weeks of gestation, affects 5-18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, which accounts for 70% of preterm births, is caused by multiple pathological processes. The authors review the current understanding of these mechanisms, including intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. Progesterone treatment has shown promise in preventing preterm labor in at-risk patients. The complexity of preterm labor, involving multiple etiologies and pathologies, presents significant challenges for diagnosis, treatment, and prevention. High-throughput techniques and systems biology are expected to enhance understanding and improve outcomes.Preterm birth, defined as delivery before 37 weeks of gestation, affects 5-18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, which accounts for 70% of preterm births, is caused by multiple pathological processes. The authors review the current understanding of these mechanisms, including intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. Progesterone treatment has shown promise in preventing preterm labor in at-risk patients. The complexity of preterm labor, involving multiple etiologies and pathologies, presents significant challenges for diagnosis, treatment, and prevention. High-throughput techniques and systems biology are expected to enhance understanding and improve outcomes.