Epidemiologic data show that women who deliver prematurely often have a personal and/or family history of preterm birth (PTB) and that racial and ethnic differences influence the incidence of PTB. This may indicate genetic predisposition to PTB. However, since races and ethnic groups tend to share environmental factors (exposure to toxins, living conditions, diet, smoking), epidemiologic data may just confirm environmental influences on PTB. Alternatively, PTB may represent a consequence of gene-environment interactions. Infection and inflammation correlate with increased risk for preterm premature rupture of amniotic membranes (PPROM) and PTB. Immunomodulatory molecules and their receptors regulate these processes and many of them are products of polymorphic genes. Single nucleotide polymorphisms (SNPs) of a gene may lead to a differential expression of its product. So far, SNPs for several genes have been implicated in PTB. If it is confirmed that polymorphism(s) in particular gene(s) correlates with PTB, it may become possible to develop targeted diagnostic and therapeutic approaches tailored towards unique genetic characteristics of a mother/fetus pair.