During this decade, major advances have been made in the development of new mouse breeds and their transplantation with human stem cells (from umbilical cord blood cells) that may effectively mimic the human immune system or show human signs of disease upon infection. The combination of studies in these mice with those in mice that are defective in interferon production or receptors have led to insights into the mechanisms of dengue pathogenesis (Bente et al. 2005; Kuruvilla et al. 2007; Kyle et al. 2007; Shresta et al. 2006) . Thus far, none of these models develop DHF and the production of DENV-specific antibodies has been low or undetectable. However, others have shown that mice engrafted with human hematopoietic cells can be effectively used to study pathogenesis of viruses for which no other models exist (Melkus et al. 2006; Watanabe et al. 2007) . It is anticipated that after adaptation of this system to DENV infection by multiple strains, with the acquisition of DENV-specific, functional B and T cells, that the signs of DHF might appear in these "humanized" mice. This would finally allow for the measurement of the many effects of immunopathogenesis, including the protective cross-immunity created by serial infection and the evaluation of many basic questions, such as dosedependence of infection, the relevance of mosquito factors to infection (e.g., salivary gland proteins) and the role of other cells as primary targets of infection (e.g., endothelial cells). Most importantly, this model could allow for the immediate testing of antivirals and vaccine candidates, where effective systems for testing products before human use have been lacking.