Rates of preterm birth have continued to rise despite intensive research efforts over the last several decades. A woman who has a spontaneous preterm birth is at high risk for a subsequent preterm birth. Studies have identified clinical, sonographic, and biochemical markers that help to identify the women at highest risk. Determining cervical length and measuring cervicovaginal fibronectin have been proposed as useful tools for evaluating women at risk of preterm birth and may identify those who might benefit from a timely course of antenatal corticosteroids, but effective interventions to prevent preterm birth remain elusive. In the prevention of recurrent spontaneous preterm birth, recent trials have confirmed the use of progesterone beginning in the second trimester as an effective intervention. Optimal management of women with a history of spontaneous preterm birth includes a thorough review of the obstetric, medical, and social history, with attention to potentially reversible causes of preterm birth (eg, smoking cessation, acute infections, strenuous activities), accurate ultrasound dating, consideration of progesterone therapy beginning at 16–20 weeks of gestation, and close surveillance during the pregnancy for evolving findings. Results from the ongoing trials of cerclage as an interventional therapy and omega-3 fatty acid supplementation as a preventive therapy will provide additional knowledge for the optimal management of these high-risk women.