AbstractDEAD‐box proteins are ubiquitous in RNA‐mediated processes and function by coupling cycles of ATP binding and hydrolysis to changes in affinity for single‐stranded RNA. Many DEAD‐box proteins use this basic mechanism as the foundation for a version of RNA helicase activity, efficiently separating the strands of short RNA duplexes in a process that involves little or no translocation. This activity, coupled with mechanisms to direct different DEAD‐box proteins to their physiological substrates, allows them to promote RNA folding steps and rearrangements and to accelerate remodeling of RNA–protein complexes. This review will describe the properties of DEAD‐box proteins as RNA helicases and the current understanding of how the energy from ATPase activity is used to drive the separation of RNA duplex strands. It will then describe how the basic biochemical properties allow some DEAD‐box proteins to function as chaperones by promoting RNA folding reactions, with a focus on the self‐splicing group I and group II intron RNAs. WIREs RNA 2011 2 135–152 DOI: 10.1002/wrna.50This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry RNA-Based Catalysis > Miscellaneous RNA‐Catalyzed Reactions RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition