In addition of the protein coding information viral RNA genomes code functional information in structurally conserved units termed functional RNA domains. These RNA domains play essential roles in the viral cycle. Members of the Flaviviridae family are responsible of important worldwide human diseases (e.g. hepatitis C, dengue, zika, west Nile fever, among others). Their genome consists in a (+) single stranded RNA molecule, which contains numerous highly structurally conserved RNA domains. They represent a good model to study and characterize the functional roles of RNA domains in the regulation of essential viral processes (e.g. translation, replication). Understanding the molecular mechanisms behind their function is essential to understand the viral infective cycle. Interfering with the function of the genomic RNA domains offers a potential means of developing antiviral strategies. Nucleic acids tools and in particular aptamers are good candidates for targeting structural RNA domains. Besides its potential as therapeutics, aptamers also provides an excellent means for investigating the functionality of RNA domains in viral genomes.