This article focuses on the influence of gene-environment interaction on pregnancy outcome. In particular, we focus on those adverse outcomes related to subclinical infection and the resultant inflammation of gestational tissues. We identify genetic association studies on pregnancy-related disorders with an infectious/inflammatory etiology. All studies in this field have focused on spontaneous preterm delivery and/or preterm and premature rupture of membranes. We discuss those articles where an environmental (infectious) exposure was studied in relation to genetic variability. In these studies, infectious exposure was defined as altered vaginal flora or bacterial vaginosis (BV). Maternal genomic variations influence both tumor necrosis factor-alpha and interleukin-1beta response to BV-related organisms (anaerobic Gram-negative bacteria and Gardnerella vaginalis in particular) in the vagina and the risk of spontaneous preterm birth. Further studies are warranted to confirm these associations, stratify disease risk, and delineate interventions for achieving population health benefits.