Preterm birth is one of the leading causes of infant mortality and the leading cause of infant morbidity in the United States. It accounts for >70% of neonatal deaths and almost half of long-term neurological disabilities. The Centers for Disease Control and Prevention (CDC) is collaborating with state health departments, universities, communities, and healthcare providers to understand why preterm births occur and how to address preterm birth risk factors. These collaborations include identification of genetic and other biological markers for the early detection of women at high risk of preterm birth; improving understanding of the relationships among psychosocial stress, immune and inflammatory responses, and preterm risk; and designing community strategies to improve the health of pregnant women. By conducting public health research activities that explore the genetic, biological, clinical, behavioral, social, and community determinants of preterm birth, CDC will continue to elucidate the complex interactions of these factors and how they influence preterm birth.