Dengue poses an increasing threat to public health worldwide. Studies conducted over the past several decades have improved our knowledge of the mechanisms of dengue virus translation and replication. New methodologies have facilitated advances in our understanding of the RNA elements and viral and host factors that modulate dengue virus replication and translation. This review integrates research findings and explores future directions for research into the cellular and molecular mechanisms of dengue virus infection. Lessons learned from dengue virus will inform approaches to other viruses and expand our understanding of the ways in which viruses co-opt host cells during the course of infection. In addition, knowledge about the molecular mechanisms of dengue virus translation and replication and the role of host cell factors in these processes will facilitate development of antiviral strategies.