Dengue (DEN) has emerged as one of the most important viruses that cause human disease and the virus is currently responsible for thousands of deaths globally each year. The severity of the disease is further exacerbated by the lack of both an effective DEN virus vaccine and antiviral drugs, and the treatment of infected individuals is by fluid replacement and supportive therapy. The only method that is currently available to control infection by the virus is mosquito control.  In this review we will discuss the current understanding of the DEN virus replication and speculate how this knowledge will be used in the development of specific antiviral strategies to control DEN virus infection.