Positive-strand RNA viruses are important human, animal and plant pathogens that are defined by their single-stranded positive-sense RNA genomes. In recent years, it has become increasingly evident that interactions that occur between distantly positioned RNA sequences within these genomes can mediate important viral activities. These long-range intragenomic RNA-RNA interactions involve direct nucleotide base pairing and can span distances of thousands of nucleotides. In this Review, we discuss recent insights into the structure and function of these intriguing genomic features and highlight their diverse roles in the gene expression and genome replication of positive-strand RNA viruses.