Dengue is a human disease which may be fatal in its hemorrhagic form. How dengue virus- and host-specified factors underlie virulence and pathogenesis is poorly understood. An immunological disorder is thought to be involved in dengue physiological symptoms. Whether the immune response is deleterious or beneficial to the host remains a matter of debate. In this review, we summarized developments in research on viral pathogenesis in the context of apoptosis triggered by dengue virus infection. Apoptosis, an active process of cell destruction, is one of the important consequences of dengue virus infection in vitro and in vivo. Dengue virus replication induces apoptosis in mouse neurons and human hepatocytes. The ability to activate this genetically programmed cell death pathway is dependent on both viral and cellular determinants.