RNA is an extraordinary molecule that can function as a regulator, informational molecule and catalyst. The breathtaking spectrum and exquisite regulation of biological functions directed by RNA is in part mediated by the ability of RNA to form unique, versatile and dynamic secondary and tertiary structures. During flavivirus infection linear and circular forms of the viral RNA exist. Although the different flaviviral RNA conformations are thought to facilitate viral gene expression and infectivity, how, when, where and why the viral genomes undergo such RNA acrobatics is less clear. Using high-throughput, biochemical and biophysical approaches our long-term goal is to dissect the role of RNA structures in the Zika virus genome to direct the switch between viral translation, replication and assembly, and the ability of Zika virus to successfully replicate in vertebrate and invertebrate hosts.