The completion of the first draft of the human genome sequence (Lander et al., 2001) and increasing information about the genome’s function have provided new opportunities for the investigation of human health and disease. Likewise, results from the exploration of human genetic variation through the International HapMap Project, spearheaded by The National Human Genome Research Institute (The International HapMap Consortium, 2003), will furnish researchers with a powerful tool for identifying variants that contribute to common diseases. This information will be especially useful when it is combined with reliable, cost-effective, high-through-put methods that can be used to genotype these variants in large population samples (Shi, 2002).

In parallel, there is a growing recognition that changes in the earth’s environment, in combination with genetic susceptibility, may contribute to many chronic diseases and may hold the key to reversing the course of some diseases (Chakravarti and Little, 2003). The improved methods for measuring nongenetic factors and environmental exposures promise to extend the scope of epidemiological investigation (Weaver et al., 1998).

Together, these developments present an exciting opportunity to address unanswered questions related to the complex contributions of genes, the environment, and gene-gene and gene-environment interactions to complex human diseases, including preterm birth. This chapter provides a review of recent progress in understanding the genetics of preterm birth, summarizes important methodological issues, and highlights areas for future research.