Preterm birth, occurring before 37 weeks of gestation, affects 5-18% of pregnancies and is a leading cause of neonatal mortality and morbidity. Spontaneous preterm labor, responsible for 70% of preterm births, is a complex syndrome with multiple underlying pathologic processes. The article reviews the mechanisms of preterm labor, including intra-amniotic infection, decidual senescence, and maternal-fetal immune tolerance disruption. It highlights the role of progesterone in maintaining uterine quiescence and the challenges in preventing preterm labor. Intra-amniotic infection, often subclinical, is a significant cause of preterm labor. Bacteria from the lower genital tract can ascend into the amniotic cavity, triggering an inflammatory response that leads to preterm labor. Decidual senescence, a loss of decidual function, is also implicated in preterm labor. Vascular dysfunction, such as placental lesions and spiral artery failure, can contribute to preterm labor by impairing placental perfusion. Maternal-fetal immune tolerance is crucial for successful pregnancy, and its breakdown can lead to preterm labor. The article emphasizes the need for understanding the complex interplay of genetic, environmental, and immunological factors in preterm labor. Progesterone therapy has shown promise in preventing preterm birth in certain high-risk patients, but its efficacy in addressing the underlying causes remains unclear. The article also discusses other mechanisms, such as uterine overdistension, maternal stress, and microbial-induced inflammation. Advances in understanding these mechanisms have led to improved prevention strategies, including the use of vaginal progesterone and cervical cerclage. However, further research is needed to develop more effective interventions. The study underscores the importance of identifying biomarkers and understanding the pathophysiology of preterm labor to improve outcomes for both mothers and infants. The complexity of preterm labor requires a multidisciplinary approach, integrating clinical, genetic, and immunological research to address this significant health challenge.Preterm birth, occurring before 37 weeks of gestation, affects 5-18% of pregnancies and is a leading cause of neonatal mortality and morbidity. Spontaneous preterm labor, responsible for 70% of preterm births, is a complex syndrome with multiple underlying pathologic processes. The article reviews the mechanisms of preterm labor, including intra-amniotic infection, decidual senescence, and maternal-fetal immune tolerance disruption. It highlights the role of progesterone in maintaining uterine quiescence and the challenges in preventing preterm labor. Intra-amniotic infection, often subclinical, is a significant cause of preterm labor. Bacteria from the lower genital tract can ascend into the amniotic cavity, triggering an inflammatory response that leads to preterm labor. Decidual senescence, a loss of decidual function, is also implicated in preterm labor. Vascular dysfunction, such as placental lesions and spiral artery failure, can contribute to preterm labor by impairing placental perfusion. Maternal-fetal immune tolerance is crucial for successful pregnancy, and its breakdown can lead to preterm labor. The article emphasizes the need for understanding the complex interplay of genetic, environmental, and immunological factors in preterm labor. Progesterone therapy has shown promise in preventing preterm birth in certain high-risk patients, but its efficacy in addressing the underlying causes remains unclear. The article also discusses other mechanisms, such as uterine overdistension, maternal stress, and microbial-induced inflammation. Advances in understanding these mechanisms have led to improved prevention strategies, including the use of vaginal progesterone and cervical cerclage. However, further research is needed to develop more effective interventions. The study underscores the importance of identifying biomarkers and understanding the pathophysiology of preterm labor to improve outcomes for both mothers and infants. The complexity of preterm labor requires a multidisciplinary approach, integrating clinical, genetic, and immunological research to address this significant health challenge.