The preterm birth rate exceeds 12% in the United States, and preterm birth continues to be a clinical and public health challenge globally. Even though preterm birth is a major contributor to infant mortality and lifelong morbidity, there are few effective strategies to predict preterm birth and few clinical interventions to prevent it. Genomic research approaches that identify risk factors at the intersection of genetics and the environment will likely provide insights. Both genetic and environmental factors are known to contribute to the racial disparity seen in preterm birth. Through the identification of relevant gene-environment interactions that contribute to preterm birth and may underlie the racial disparity in preterm birth, research that will translate to clinical practice and ultimately prevent a number of preterm births is possible. Mt Sinai J Med 77:160–165, 2010. © 2010 Mount Sinai School of Medicine