Evidence that host genetic factors play a major role in susceptibility or resistance to many infectious diseases is increasing, due to major advances in genetic epidemiological methodology. Recent human genome mapping information and the identification of a large number of candidate genes provide the tools for such studies. The information obtained is important for understanding the pathogenesis of disease and for the design of preventive and therapeutic strategies. In the study of Chlamydia trachomatis disease pathogenesis, much research focuses on how bacterial factors modulate the immune response and thus contribute to the disease process. It is likely, however, that host factors also play a role, and therefore susceptibility to disease is the result of an environmental effect set against a background of genetic factors. This review outlines the evidence for the contribution of host genetic factors to susceptibility to C. trachomatis disease in humans.