Viremia is one of the features of dengue virus infection among the flaviviruses. Dengue virus infection results in a spectrum of clinical symptoms, ranging from undifferentiated flu-like illness, mild dengue fever, to dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), a life-threatening illness. Several mechanisms have been hypothesized based primarily on data collected from post-acute clinical phase to account for DHF/DSS. Lack of a suitable animal model for DHF/DSS has hindered progress in defining the etiology of DHF/DSS. Levels of circulating dengue virus have been well-correlated to severe dengue disease. However, the cell lineage(s) serving as a primary target for the source of viremia are largely unknown. Results from in vivo and in vitro pilot studies using molecular and more advanced technologies reveal that dengue virus appears to be associated with platelets and the megakaryocytic lineage. The observation may partially explain the dysfunction of platelets observed in dengue affected patients.